Appl Biochem Biotechnol. 2022 Apr 23. doi: 10.1007/s12010-022-03923-7. Online ahead of print.

ABSTRACT

The negative changes of obesity to the locomotor system are a major concern in the current scenario, where obesity and metabolic syndrome are recurrent in Western societies. A physical exercise is an important tool as a way to rehabilitate obesity, highlighting whole-body vibration, as it is an easy-access modality with few restrictions. In this sense, we sought to evaluate the effect of whole-body vibration on the extensor digitorum longus muscle on a monosodium glutamate-induced obesity model. The main findings of the present study are related to the ability of the treatment with vibration to reduce the obesogenic characteristics and slow down the dyslipidemic condition of the animals. Likewise, the vibration promoted by the vibrating platform was essential in the recovery of the muscle structure, as well as the recovery of the muscle's oxidative capacity, initially compromised by obesity.

PMID:35460454 | DOI:10.1007/s12010-022-03923-7

Exp Physiol. 2022 Apr 9. doi: 10.1113/EP089883. Online ahead of print.

ABSTRACT

NEW FINDINGS: What is the central question of this study? Can an anaemic state modify adiposity and metabolic parameters in hypothalamic obese rats? What is the main finding and its importance? Hypothalamic obese rats do not display iron deficiency. However, the pharmacological induction of anaemia in hypothalamic obese rats resulted in reduced adiposity, characterized by a decrease in subcutaneous white and brown adipose tissue depots. These findings suggest that iron imbalance in obesity may elevate lipolysis.

ABSTRACT: Iron imbalance is frequent in obesity. Herein, we evaluated the impact of anaemia induced by phenylhydrazine on adiposity and metabolic state of hypothalamic obese rats. Hypothalamic obesity was induced by high doses of monosodium glutamate (MSG; 4 g/kg) administered to neonatal male rats (n = 20). Controls (CTL; non-obese rats) received equimolar saline (n = 20). Rats were weaned at 21 days of life. At 70 days, half of the rats received three intraperitoneal doses of phenylhydrazine (PHZ; 40 mg/kg/dose) or saline solution. Body weight and food intake were followed for 4 weeks after PHZ administration. At 92 days, rats were killed and blood was collected for microcapillary haematocrit (Hct) analysis and plasma quantification of glucose, triglycerides, total cholesterol and iron levels. The liver, the spleen, and the white (WAT) and brown (BAT) adipose tissues were excised, weighed and used for histology. MSG-treated rats developed obesity, hypertriglyceridaemia and insulin resistance, compared to CTL rats, without changes in iron levels and Hct. PHZ administration reduced plasma iron levels and promoted similar tissue injuries in the spleen and liver from MSG and CTL rats. However, in MSG-treated rats, PHZ decreased fasting glucose levels and Hct, as well as diminishing the subcutaneous WAT and BAT mass. Although MSG-obesity does not affect plasma iron levels and Hct by itself, PHZ-induced anaemia associated with obesity induces a marked drop in subcutaneous WAT and BAT mass, suggesting that iron imbalance may lead to increased lipolytic responses in obese rats, compared to lean rats.

PMID:35396880 | DOI:10.1113/EP089883

Zhongguo Zhong Yao Za Zhi. 2022 Mar;47(5):1307-1315. doi: 10.19540/j.cnki.cjcmm.20211210.402.

ABSTRACT

This paper aims to study the effect of Xiangqin Jiere Granules(XQ) on lipid metabolism and chronic inflammation in different obesity model mice. The monosodium glutamate(MSG) obese mouse model was established by subcutaneous injection of MSG in newborn mice, and the high fat diet(HFD) obese mouse model was established by feeding adult mice with HFD. The normal mice were assigned into the control group; the MSG obese mice were assigned into MSG model group, XQ4.5 group(Xiangqin Jiere Granu-les, 4.5 g·kg~(-1)), XQ22.5 group(Xiangqin Jiere Granules, 22.5 g·kg~(-1)); the HFD obese mice were assigned into HFD model group, XQ4.5 group, and XQ22.5 group. The mice were intragastrically administrated with saline or XQ for 5 weeks. After that, the body weight, visceral fat mass, liver and thymus weight, and the organ indexes in each group were measured. The levels of triglyceride(TG), total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-c) in serum and liver tissue were detected by the kits. The mRNA expression levels of acetyl CoA carboxylase 1(ACC1), fatty acid synthetase(FAS), diacylgycerol acyltransferase 1(DGAT1) and hepatic lipase(HTGL) involved in lipid metabolism in mouse liver tissue were detected by quantitative real-time PCR(qPCR). The protein levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in serum were detected by ELISA, and the mRNA levels of TNF-α and IL-6 in liver tissue were detected by qPCR. Compared with the control group, MSG and HFD mice showed increased body weight, abdominal circumference, Lee index and visceral fat mass as well as elevated levels of TG, TC, and LDL-c in serum. The model mice had up-regulated gene levels of ACC1, FAS and DGAT1 while down-regulated gene level of HTGL in the liver. Furthermore, the mRNA and protein levels of IL-6 increased in the model mice. Compared with the model mice, XQ treatment decreased the body weight, abdominal circumference, Lee index, and visceral fat mass, lowered the levels of TG, TC, and LDL-c in se-rum, down-regulated the gene levels of ACC1, FAS, and DGAT1 in liver tissue, up-regulated the gene level of HTGL, and down-regulated the mRNA and protein levels of IL-6. To sum up, XQ has good therapeutic effect on different obesity model mice. It can improve lipid metabolism and reduce fat accumulation in obese mice by regulating the enzymes involved in lipid metabolism, and alleviate obesity-related chronic low-grade inflammation.

PMID:35343159 | DOI:10.19540/j.cnki.cjcmm.20211210.402

Diabetes Metab Syndr Obes. 2021 Oct 27;14:4351-4360. doi: 10.2147/DMSO.S335526. eCollection 2021.

ABSTRACT

PURPOSE: To investigate resistance to diet-induced obesity (DIO) and monosodium glutamate (MSG)-induced obesity as well as the underlying mechanisms.

METHODS: Newborn mice were used to construct DIO and MSG-induced obesity models. Obesity indices, such as body weight, body length, Lee index, body temperature, food intake, fat weight, and leptin level, were examined. Mice that did not exhibit obesity were defined as the obesity-resistant group. The morphological changes of white adipose tissue were observed by hematoxylin and eosin staining, and expression levels of PR domain containing 16 (Prdm16) and uncoupling protein-1 (Ucp-1) in white adipose tissue were measured by Western blot.

RESULTS: Obesity-resistant mice fed a high-fat diet showed resistance beginning at week 5 along with lower weights and lengths than those in the obesity group from weeks 5 to 12. MSG-induced obesity-resistant mice showed features consistent with resistance to obesity from week 1 along with higher body lengths relative to the obesity group; however, the weight difference was not significant until week 10, when body weights decreased significantly in obesity-resistant mice. The Lee index was lower in obesity-resistant mice than in the obesity group and the normal group, further suggesting obesity resistance. Additionally, obesity-resistant mice showed higher levels of leptin, whereas obese mice induced by a high-fat diet showed leptin resistance. Furthermore, Prdm16 and Ucp-1 levels were both downregulated in the obesity group and upregulated in obesity-resistant mice, showing that white fat browning was highest in obesity-resistant mice.

CONCLUSION: The phenotypes of mice with DIO and MSG-induced obesity differed. Obesity resistance might be related to Prdm16 and Ucp-1-mediated white adipocyte browning.

PMID:34737591 | PMC:PMC8558318 | DOI:10.2147/DMSO.S335526

Life Sci. 2021 Dec 1;286:120033. doi: 10.1016/j.lfs.2021.120033. Epub 2021 Oct 8.

ABSTRACT

AIMS: Sepsis is a potentially fatal systemic inflammatory response and its underlying pathophysiology is still poorly understood. Studies suggest that obesity, a component of metabolic syndrome (MS), is associated with sepsis survival. Therefore, this study focused on investigating the influence of MS on mortality and cardiovascular dysfunction induced by sublethal cecal ligation and puncture (SL-CLP).

MAIN METHODS: Newborn Swiss mice received monosodium glutamate (MSG) (4 mg kg^-1 day^-1, s.c.) during the first 5 d of life for MS induction, while the control pups received equimolar saline solution. On the 75th day, SL-CLP was used to induce mild sepsis (M-CLP) in the MS (MS-M-CLP) and control (SAL-M-CLP) mice. The effect of MS on sepsis in mice was assessed by determining the survival rate and quantification of nitric oxide (NO) in the plasma, and associating this data with hematological and cardiovascular parameters.

KEY FINDINGS: MS improved the survival of septic mice, preventing impairment to hematological and cardiovascular parameters. In addition, MS attenuated plasmatic NO increase, which is a typical feature of sepsis.

SIGNIFICANCE: These findings provide new insights into the relationship between obesity and mild sepsis in mice, thus revealing an approach in favor of the "obesity paradox."

PMID:34627775 | DOI:10.1016/j.lfs.2021.120033

Nat Metab. 2021 Sep;3(9):1189-1201. doi: 10.1038/s42255-021-00454-z. Epub 2021 Sep 22.

ABSTRACT

Umami refers to the savoury taste that is mediated by monosodium glutamate (MSG) and enhanced by inosine monophosphate and other nucleotides. Umami foods have been suggested to increase the risk for obesity and metabolic syndrome but the mechanism is not understood. Here we show that MSG induces obesity, hypothalamic inflammation and central leptin resistance in male mice through the induction of AMP deaminase 2 and purine degradation. Mice lacking AMP deaminase 2 in both hepatocytes and neurons are protected from MSG-induced metabolic syndrome. This protection can be overcome by supplementation with inosine monophosphate, most probably owing to its degradation to uric acid as the effect can be blocked with allopurinol. Thus, umami foods induce obesity and metabolic syndrome by engaging the same purine nucleotide degradation pathway that is also activated by fructose and salt consumption. We suggest that the three tastes-sweet, salt and umami-developed to encourage food intake to facilitate energy storage and survival but drive obesity and diabetes in the setting of excess intake through similar mechanisms.

PMID:34552272 | DOI:10.1038/s42255-021-00454-z

Pharmaceutics. 2021 Jul 29;13(8):1173. doi: 10.3390/pharmaceutics13081173.

ABSTRACT

Endothelial dysfunction in obesity plays a key role in the development of cardiovascular diseases, and it is characterized by increased vascular tonus and oxidative stress. Thus, this study aimed to investigate the vasodilatory and antioxidant activities of Mandevilla moricandiana ethyl acetate fraction and subfractions. Vascular effects were investigated on aorta isolated from control and monosodium glutamate (MSG) induced-obese Wistar rats, and antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) methods. The ethyl acetate fraction (MMEAF) induced a concentration-dependent vasodilation on aortic rings through the NO pathway, with the involvement of histamine H1 and estrogen ERα receptors and showed potent antioxidant activity. In aorta of MSG obese rats, maximal relaxation to acetylcholine was increased in the presence of MMEAF (3 µg/mL), indicating that MMEAF ameliorated obesity-induced endothelial dysfunction. Quercetin and kaempferol aglycones and their correspondent glycosides, as well as caffeoylquinic acid derivatives, A-type procyanidin trimer, ursolic and oleanolic triterpenoid acids were identified in subfractions from MMEAF and seem to be the metabolites responsible for the vascular and antioxidant activities of this fraction.

PMID:34452134 | PMC:PMC8401510 | DOI:10.3390/pharmaceutics13081173

Front Physiol. 2021 Jun 25;12:672027. doi: 10.3389/fphys.2021.672027. eCollection 2021.

ABSTRACT

The vagus nerve (VN) and spleen represent a complex interface between neural and immunological functions, affecting both energy metabolism and white adipose tissue (WAT) content. Here, we evaluated whether vagal and splenic axis participates in WAT mass regulation in obese and non-obese male Wistar rats. High doses of monosodium glutamate (M; 4 g/Kg) were administered during the neonatal period to induce hypothalamic lesion and obesity (M-Obese rats). Non-obese or Control (CTL) rats received equimolar saline. At 60 days of life, M-Obese and CTL rats were randomly distributed into experimental subgroups according to the following surgical procedures: sham, subdiaphragmatic vagotomy (SV), splenectomy (SPL), and SV + SPL (n = 11 rats/group). At 150 days of life and after 12 h of fasting, rats were euthanized, blood was collected, and the plasma levels of glucose, triglycerides, cholesterol, insulin, and interleukin 10 (IL10) were analyzed. The visceral and subcutaneous WAT depots were excised, weighed, and histologically evaluated for number and size of adipocytes as well as IL10 protein expression. M-Obese rats showed higher adiposity, hyperinsulinemia, hypertriglyceridemia, and insulin resistance when compared with CTL groups (p < 0.05). In CTL and M-Obese rats, SV reduced body weight gain and triglycerides levels, diminishing adipocyte size without changes in IL10 expression in WAT (p< 0.05). The SV procedure resulted in high IL10 plasma levels in CTL rats, but not in the M-Obese group. The splenectomy prevented the SV anti-adiposity effects, as well as blocked the elevation of IL10 levels in plasma of CTL rats. In contrast, neither SV nor SPL surgeries modified the plasma levels of IL10 and IL10 protein expression in WAT from M-Obese rats. In conclusion, vagotomy promotes body weight and adiposity reduction, elevating IL10 plasma levels in non-obese animals, in a spleen-dependent manner. Under hypothalamic obesity conditions, VN ablation also reduces body weight gain and adiposity, improving insulin sensitivity without changes in IL10 protein expression in WAT or IL10 plasma levels, in a spleen-independent manner. Our findings indicate that the vagal-spleen axis influence the WAT mass in a health state, while this mechanism seems to be disturbed in hypothalamic obese animals.

PMID:34248663 | PMC:PMC8269450 | DOI:10.3389/fphys.2021.672027

Life Sci. 2021 Sep 1;280:119751. doi: 10.1016/j.lfs.2021.119751. Epub 2021 Jun 23.

ABSTRACT

AIMS: Obesity is associated with a spectrum of hepatic abnormalities that can be experimentally induced by injections of monosodium glutamate (MSG) in neonatal rodents. We investigated the protective actions of the repeated therapy with 4-phenylselenyl-7-chloroquinoline (4-PSQ), a quinoline derivative containing selenium, on damage to the liver triggered by early postnatal administration of MSG in male Wistar rats.

MAIN METHODS: Neonatal rats received MSG (4 g/kg, subcutaneous route) or saline (1 ml/kg) from 5 to 14 postnatal day (PND) to induce obesity with consequent damages in the liver. 4-PSQ treatment (5 mg/kg) or canola oil (1 ml/kg) was administered from 60 to 76 PND by the intragastric route. On 76 PND, animals were anesthetized for blood and liver collection. Plasma markers of hepatic function, hepatic lipoperoxidation levels and histology analysis of liver tissue were assessed.

KEY FINDINGS: Our data revealed that treatment with 4-PSQ reverted the increase in plasma transaminases activities observed in MSG rats. Treatment with 4-PSQ reduced plasma lactate levels in obese rats. In the liver, MSG elevated the content of lipoperoxidation which was reverted by 4-PSQ administrations. Lastly, 4-PSQ therapy attenuated the histological alterations induced by MSG.

SIGNIFICANCE: Together, the results indicate a hepatoprotective action of repeated treatment with 4-PSQ in obese rats.

PMID:34174321 | DOI:10.1016/j.lfs.2021.119751

J Food Biochem. 2021 Jun 22:e13819. doi: 10.1111/jfbc.13819. Online ahead of print.

ABSTRACT

Monosodium glutamate (MSG) has been traditionally used as a flavor enhancer and is added to many foods. The chronic consumption of MSG has been suggested as causing toxicity, inflammation, obesity, type 2 diabetes, and pre-malignant changes. The use of medicinal plants and their products, such as ginger, against the effects of MSG has been suggested to have a protective effect. To evaluate the anti-inflammatory activity of ginger against the effects of MSG, we conducted a serial inflammatory analysis of MSG- and ginger-treated rats, focusing particularly on liver pathology. The consumption of ginger as an unconventional therapy against the effects of MSG resulted in significant anti-inflammatory activity. We found that it was possible to diagnose MSG-associated inflammatory pathogenesis using inflammatory mediators. Ginger consumption produced protective effects on health, minimized adverse effects, and may be applicable for food development and the treatment of many inflammatory diseases. PRACTICAL APPLICATIONS: The chronic administration of monosodium glutamate (MSG) as a flavor enhancer has been suggested to produce toxicity, inflammation, and pre-malignant changes in organs. Ginger has protective effects, with potent anti-inflammatory and anti-fibrotic activity against MSG administration. This study is the first to report that ginger modulated the inflammatory and fibrotic effects of MSG and improved immunological indices reflecting the involvement of inflammatory and fibrotic markers and polysaccharide content in the activation of macrophages. These findings support the further use of ginger as a supplement for food enhancement and as an anti-fibrotic, anti-inflammatory, and therapeutic agent in pharmaceutical therapies against autoimmune and inflammatory diseases, such as rheumatoid arthritis, lupus, and ulcerative colitis, as well as MSG-associated inflammatory diseases.

PMID:34159624 | DOI:10.1111/jfbc.13819

Front Endocrinol (Lausanne). 2021 Jun 4;12:660793. doi: 10.3389/fendo.2021.660793. eCollection 2021.

ABSTRACT

Metformin is an antidiabetic drug used for the treatment of diabetes and metabolic diseases. Imbalance in the autonomic nervous system (ANS) is associated with metabolic diseases. This study aimed to test whether metformin could improve ANS function in obese rats. Obesity was induced by neonatal treatment with monosodium L-glutamate (MSG). During 21-100 days of age, MSG-rats were treated with metformin 250 mg/kg body weight/day or saline solution. Rats were euthanized to evaluate biometric and biochemical parameters. ANS electrical activity was recorded and analyzed. Metformin normalized the hypervagal response in MSG-rats. Glucose-stimulated insulin secretion in isolated pancreatic islets increased in MSG-rats, while the cholinergic response decreased. Metformin treatment normalized the cholinergic response, which involved mostly the M3 muscarinic acetylcholine receptor (M3 mAChR) in pancreatic beta-cells. Protein expression of M3 mAChRs increased in MSG-obesity rats, while metformin treatment decreased the protein expression by 25%. In conclusion, chronic metformin treatment was effective in normalizing ANS activity and alleviating obesity in MSG-rats.

PMID:34149616 | PMC:PMC8212417 | DOI:10.3389/fendo.2021.660793

Braz J Med Biol Res. 2021 May 31;54(9):e11116. doi: 10.1590/1414-431X2020e11116. eCollection 2021.

ABSTRACT

The interplay between obesity and gastrointestinal (GI) motility is contradictory, and the transgenerational influence on this parameter is unknown. We aimed to evaluate the GI function in a model of paternal obesity and two subsequent generations of their male offspring. Newborn male rats were treated with monosodium glutamate (MSG) and composed the F1 generation, while control rats (CONT) received saline. At 90 days, male F1 were mated with non-obese females to obtain male offspring (F2), which later mated with non-obese females for obtaining male offspring of F3 generation. Lee Index analysis was adopted to set up the obesity groups. Alternating current biosusceptometry (ACB) technique was employed to calculate GI transit parameters: mean gastric emptying time (MGET), mean cecum arrival time (MCAT), mean small intestinal transit time (MSITT), and gastric frequency and amplitude of contractions. Glucose, insulin, and leptin levels and duodenal morphometry were measured. F1 obese rats showed a decrease in the frequency and amplitude of gastric contractions, while obese rats from the F2 generation showed accelerated MGET and delayed MCAT and MSITT. Glucose and leptin levels were increased in F1 and F2 generations. Insulin levels decreased in F1, F2, and F3 generations. Duodenal morphometry was altered in all three generations. Obesity may have paternal transgenerational transmission, and it provoked disturbances in the gastrointestinal function of three generations.

PMID:34076145 | PMC:PMC8186378 | DOI:10.1590/1414-431X2020e11116

Front Nutr. 2021 Apr 29;8:671353. doi: 10.3389/fnut.2021.671353. eCollection 2021.

ABSTRACT

Monosodium glutamate (MSG)-induced abdominal obesity, conventionally caused by hypothalamic damage, is a critical risk factor for health problem. Microbiota-gut-brain axis plays important roles in a variety of metabolic diseases. However, whether gut microbiota is involved in the pathogenesis for MSG-induced abdominal obesity and the effect of quercetin on it remains unclear. Herein, we find that MSG-induced gut microbiota dysbiosis contributes to neuronal damage in the hypothalamus, as indicated by antibiotics-induced microbiota depletion and co-house treatment. Inspired by this finding, we investigate the mechanism in-depth for MSG-induced abdominal obesity. Liver transcriptome profiling shows retinol metabolism disorder in MSG-induced abdominal obese mice. In which, retinol saturase (RetSat) in the liver is notably up-regulated, and the downstream lipogenesis is correspondingly elevated. Importantly, microbiota depletion or co-house treatment eliminates the difference of RetSat expression in the liver, indicating gut microbiota changes are responsible for liver retinol metabolism disorder. Moreover, this study finds dietary quercetin could modulate MSG-induced gut microbiota dysbiosis, alleviate hypothalamic damage and down-regulate liver RetSat expression, thus ameliorating abdominal obesity. Our study enriches the pathogenesis of MSG-induced abdominal obesity and provides a prebiotic agent to ameliorate abdominal obesity.

PMID:33996881 | PMC:PMC8116593 | DOI:10.3389/fnut.2021.671353

Food Funct. 2021 Apr 26;12(8):3586-3596. doi: 10.1039/d1fo00073j.

ABSTRACT

Myricetin is a flavonol highly prevalent in edible vegetables and fruits, with recognized hypoglycemic and anti-obesity effects, besides great antioxidant capacity. Thus, this study sought to investigate whether myricetin is able to improve metabolic and behavioral outcomes found in monosodium l-glutamate (MSG) obese mice, a model of metabolic syndrome characterized by early hyperinsulinemia associated to obesity, dyslipidemia, hepatic steatosis, anxiety and cognitive deficit. Newborn male mice received MSG (4 mg kg-1 day-1, s.c.) on alternate days during the first 10 days of life for obesity induction, while control pups received equimolar saline solution. From postnatal day 90 to 135, MSG mice were orally treated with myricetin (50 mg kg-1 day-1) or distilled water, while control animals received vehicle. During the last week of treatment, all groups were submitted to behavioral tests: open field maze, elevated plus maze and Morris water maze. At the end of treatment, animals were euthanized for collection of liver, serum and adipose tissue fat pads. Myricetin treatment reduced the elevated serum levels of glucose and triglycerides, typically found in MSG mice, as well as restored peripheral insulin sensitivity and liver steatosis. Moreover, myricetin ameliorated the lack of thigmotaxis and exploratory behavior, but did not improve the cognitive deficit presented by MSG mice. Therefore, this study contributes to the pharmacological validation of myricetin as an affordable and healthy therapeutic adjuvant for the treatment of metabolic syndrome and most of its comorbidities.

PMID:33900338 | DOI:10.1039/d1fo00073j

Psychopharmacology (Berl). 2021 Jul;238(7):1937-1951. doi: 10.1007/s00213-021-05821-y. Epub 2021 Mar 19.

ABSTRACT

RATIONALE: Obesity is considered one of the major global health problems and increases the risk of several medical complications, such as diabetes and mental illnesses.

OBJECTIVE: The present study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on obesity parameters, behavioral and neurochemical alterations in hypothalamic obese rats.

METHODS: Male Wistar rats received subcutaneous neonatal injections of monosodium glutamate (MSG, 4g/kg) or saline. After the Lee Index evaluation, rats were divided into groups and treated with 4-PSQ (5 mg/kg, intragastric route) or canola oil once a day (post-natal days (PND) 60→76). Open-field, elevated plus-maze, forced swim task, object recognition/location memory, and stepdown inhibitory avoidance tasks were conducted from PND 66 to 74. On PND 76, rats were euthanized and epididymal fat, blood, cerebral cortex, andhippocampus were removed. Blood biochemical parameters and cortical/hippocampal acetylcholinesterase (AChE) and Na /K -ATPase activities were assessed.

RESULTS: MSG increased the Lee Index characterizing the chemically induced hypothalamic obesity model. 4-PSQ reversed the increases of epididymal fat, blood glucose, and triglyceride levels caused by MSG exposure. 4-PSQ attenuated anxiety-like and depression-like behaviors induced by neonatal administrations of MSG. Memory deficits found in MSG-obese rats were reversed by treatment with 4-PSQ. Neurochemical alterations produced by MSG evidenced by stimulation ofNa⁺/K⁺-ATPase and AChE activities in the cerebral cortex and hippocampus of rats were normalized by 4-PSQ treatment.

CONCLUSIONS: In brief, 4-PSQ therapy improved hypothalamic obesity-related parameters, as well as psychiatric symptoms, cognitive impairment, and neurochemical alterations found in obese rats.

PMID:33740091 | DOI:10.1007/s00213-021-05821-y

Acta Cir Bras. 2021 Feb 22;36(2):e360205. doi: 10.1590/ACB360205. eCollection 2021.

ABSTRACT

PURPOSE: To evaluate the influence of autonomic vagal and splenic activities on renal histomorphometric aspects in obese rats.

METHODS: Thirty male Wistar rats were used, of which, 24 received subcutaneous injections of monosodium glutamate (MSG) during the first 5 days of life (4 g/kg body weight) and six control animals received injections of saline solution (CON). Five experimental groups were organized (n = 6/group): falsely-operated control (CON-FO); falsely-operated obese (MSG-FO); vagotomized obese (MSG-VAG); splenectomized obese (MSG-SPL); vagotomized and splenectomized obese (MSG-VAG-SPL).

RESULTS: The MSG-FO group animals showed a significant reduction in body weight and nasal-anal length when compared to CON-FO group animals (p < 0.05). The MSG-VAG-SPL group showed significant reduced in most biometric parameters associated with obesity. Falsely-operated obese animals showed a significant reduction in renal weight, glomerular diameters, glomerular tuff and capsule areas and Bowman's space compared to CON-FO group animals (p < 0.05). There was a significant reduction in diameter, glomerular tuft and capsule areas, and Bowman's space in MSG-VAG, MSG-SPL, MSG-VAG-SPL groups when compared to the MSG-FO group.

CONCLUSIONS: Vagotomy associated with splenectomy induces a reduction in the adiposity and causes histological changes in the kidney of obese rats.

PMID:33624722 | PMC:PMC7902077 | DOI:10.1590/ACB360205

Nutr Res. 2021 Jan;85:40-46. doi: 10.1016/j.nutres.2020.12.007. Epub 2020 Dec 5.

ABSTRACT

Taste is a fundamental mechanism whereby compounds are detected orally, yet it is highly variable among individuals. The variability in taste that is attributable to genetics is not well-characterized despite its potential role in food selection, and therefore, eating habits that contribute to risk of overweight and obesity. In order to implicate measures of taste function and preference as potentially deterministic factors in adverse eating behaviors that lead to obesity, it must be shown that a relationship exists between genetic variation in taste receptor genes and psychophysical measures of taste in the absence high body mass index. The primary objective of this pilot study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in taste receptor genes and 3 different psychophysical measures of taste in healthy young adults. Sweet, salt, umami, fat, sour, and bitter taste receptor gene SNPs were genotyped in 49 participants (ages 24.6 ± 0.6 years) who completed testing to determine oral detection threshold (DT), suprathreshold sensitivity (ST) and taste preference (PR). A simultaneous association test was conducted between each SNP and the 3 taste outcomes (DT, ST, and PR). Twelve SNPs were associated with at least one of the 3 taste outcomes. Associations were observed between SNPs in taste receptor genes and psychophysical measures of sweet, fat, umami, and salt taste. These results suggest that differences in interindividual psychophysical measures of tastes, namely DT, ST, and PR, may be partially attributed to genetic variation in taste receptor genes. Future studies are warranted to investigate if these findings have consequences for habitual dietary intake of foods that elicit these tastes.

PMID:33444969 | DOI:10.1016/j.nutres.2020.12.007

An Acad Bras Cienc. 2020 Dec 14;92(4):e20201097. doi: 10.1590/0001-3765202020201097. eCollection 2020.

ABSTRACT

The aim was to evaluate the effects of chronic vitamin D (VD) supplementation associated with regular swimming over renal histomorphometric aspects in obese rats. Thirty Wistar male rats (5 days old) were used. Twenty four rats were given subcutaneous injections of monosodium glutamate (MSG; 4 g/kg), and six control rats were given an equimolar saline solution. At 21-days-old, the MSG-treated rats were randomly distributed among sedentary animals (S) and exercised (E, swimming; 3x/week). These groups were subdivided into groups orally supplemented with VD (12 μg/kg; 3x/week) or not supplemented (NS), totaling Five experimental groups (n = 6 rats/group): MSG, MSG-SVD, MSG-ENS, MSG-EVD and control groups. In MSG-obese rats, there was such as a decrease in the diameter of the, glomerular tuft, Bowman's capsule, Bowman's space areas, and renal cortical thickness, compared to the control group. In MSG-SVD, MSG-ENS, and MSG-EVD animals, there was an increase in the cortical thickness in relation to the MSG group. In MSG-ENS and MSG-EVD animals, there was a reduction of tubular degeneration in relation to the MSG group. We conclude that physical exercise associated with Vitamin D supplementation can prevent of renal injury, increasing the thickness of the renal cortex and decrease the tubular degeneration.

PMID:33331449 | DOI:10.1590/0001-3765202020201097

Life Sci. 2021 Feb 1;266:118846. doi: 10.1016/j.lfs.2020.118846. Epub 2020 Dec 9.

ABSTRACT

AIMS: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities. Anatomically restructuring of the gastrointestinal system has recently been an important subject of research in the treatment of MetS and closely related diseases. The aim of this study is to ensure the remission of parameters that define MetS by ileal interposition (IT) and to examine the effect of IT on plasma total GLP-1 and pancreatic GLP-1R expression.

MAIN METHODS: To induce MetS, newborn male Wistar albino rats were given MSG (4 g/mg) on days 0, 2, 4, 6, 8, and 10. The control group was injected with saline. In the 5th month, IT or sham surgery was performed on the MetS rats. The lipid levels, abdominal obesity, insulin level, OGTT, Lee index, HOMA-IR, plasma GLP-1 and pancreas GLP-1R expression were evaluated 2 months after surgery.

KEY FINDINGS: The results showed that IT significantly improved hyperinsulinemia (p = 0.013) and lipid profile (TG p = 0.0001; TCHOL p = 0.018; HDL p = 0.001). Furthermore, it normalized the Lee index (p = 0.006) and insulin resistance. The IT did not affect the secretion of the GLP-1, but the expression levels of pancreas GLP-1R were increased (p = 0.006).

SIGNIFICANCE: IT surgery corrected the MetS parameters in this rat model. The healing effects of IT surgery could be caused by mechanisms in the target tissues of insulin. The decrease in pancreatic GLP-1R levels in the MetS groups might be a compensatory response to the harmful effects of hyperinsulinemia in these groups. These results show that IT can be useful in the treatment of MetS.

PMID:33309719 | DOI:10.1016/j.lfs.2020.118846

Chin J Nat Med. 2020 Nov;18(11):827-836. doi: 10.1016/S1875-5364(20)60023-1.

ABSTRACT

Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes (T2DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate (MSG)-induced obese mice, suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance (IGT) to T2DM. In this study, we evaluated the effect of JTN on the progression of T2DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment, blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The β cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp. Thus, to investigate the underlying mechanisms of JTN in protecting β cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones (insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in β cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase (GCK), pyruvate carboxylase (PCB) and pancreas duodenum homeobox-1 (PDX-1), while down-regulating C/EBP homologous protein (Chop) expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum (ER) stress of β cells after JTN treatment. These results will provide a new insight into exploring a novel strategy of JTN for protecting β cell function and preventing the onset of pre-diabetes to T2DM.

PMID:33308603 | DOI:10.1016/S1875-5364(20)60023-1

J Musculoskelet Neuronal Interact. 2020 Dec 1;20(4):570-578.

ABSTRACT

OBJECTIVES: evaluate the effects that whole-body vibration (WBV) causes on the neuromuscular junctions and oxidative stress of the soleus muscle of obese Wistar rats.

METHODS: 32 male Wistar rats were used, 16 of which were obesity induced by monosodium glutamate, randomized into four groups: control (GC), control with WBV (GCP), obese (GO) and obese with WBV (GOP). At the 70 days old, the training on WBV was started, performed 3 times a week, during 8 consecutive weeks. At the 130 days old, the animals were euthanized and the soleus muscles were collected.

RESULTS: Regarding the analysis of the neuromuscular junctions, the obese groups had lower mean size when compared to the control groups. On the other hand, the WBV presented higher averages when compared to the groups that did not perform the training. Regarding the oxidative stress, for the lipid peroxidation there was a significant difference between obese and non-obese animals, however, there was no difference between the animals WBV and those who did not.

CONCLUSION: WBV promotes beneficial changes such as increased measurements of the structures of the neuromuscular junctions, but is not able to promote changes in the concentration of the cholinesterase enzyme in the synaptic cleft.

PMID:33265086 | PMC:PMC7716688

An Acad Bras Cienc. 2020 Nov 20;92(4):e20201382. doi: 10.1590/0001-3765202020201382. eCollection 2020.

ABSTRACT

D-pinitol is one of the major inositol found in plants and studies suggest its potential hypoglycemic and hypolipidemic actions in diabetic rodents. Here, we investigated the actions of D-pinitol on adiposity, and in lipid and glycemic homeostasis in monosodium glutamate (MSG)-obese mice. Swiss mice received daily subcutaneous injections of MSG [(4g/kg of body weight (BW)] or saline [1.25g/kg BW; control (CTL)] during their first five days of life. From 90-120 day-old, half of the MSG and CTL groups received 50 mg D-pinitol/kg BW/day (MPIN and CPIN groups) or vehicle (saline; MSG and CTL groups) by gavage. MSG mice displayed higher abdominal adiposity and hepatic triglycerides (TG) deposition, and increased hepatic expression of lipogenic genes (SREBP-1c, ACC-1 and FASN), but downregulation in AMPKα mRNA. MSG mice also exhibited hyperinsulinemia, islet hypersecretion and hypertrophy, glucose intolerance and insulin resistance. D-pinitol did not change adiposity, glucose intolerance, insulin resistance, but increased hepatic triglycerides (TG) content in MPIN mice, which was associated with increases in gene expressions of SREBP-1c and FASN, but reduction in AMPKα. Furthermore, D-pinitol enhanced insulin secretion in MPIN and CPIN groups. Therefore, D-pinitol enhanced glucose-induced insulin secretion, which may account to enhances hepatic lipogenesis and TG deposition in MPIN mice.

PMID:33237150 | DOI:10.1590/0001-3765202020201382

Tissue Cell. 2021 Feb;68:101456. doi: 10.1016/j.tice.2020.101456. Epub 2020 Oct 30.

ABSTRACT

OBJECTIVES: This study aimed to analyze the effect of whole-body vibration (WBV) on metabolic parameters using the monosodium l-glutamate (MSG) model of obesity.

METHOD: MSG-obese rats that were exposed to WBV on a vibrating platform with 60 Hz frequency, 2 mm amplitude, three times/week, 10 min/day, during eight weeks (from postnatal day (PN) 80 to PN136). Blood glucose, creatine kinases (CK and CK-MB) and lipid profile through plasma and liver levels of lipids and lipoproteins were evaluated. Morphology and oxidative stress of adipose and hepatic tissues were further evaluated.

RESULTS: When performing a WBV exercise, animals showed contrasting metabolic responses. Vibration Control group (CTL-WBV) presented a reduction in CK and liver triacylglycerol, an increase in glucose, lactate, total cholesterol, liver cholesterol, and LDL while MSG Vibration group (MSG-WBV) showed an increase in total triacylglycerol, VLDL, lactate, CK, liver cholesterol, additional liver lipid peroxidation and LDL, total cholesterol and CKMB reduction.

CONCLUSION: Even although the MSG is a model of impacting injury, the metabolic demand of WBV exercise was able to induce mobilization of substrates, highlighting the lipid mobilization in obese animals, it should be used as a metabolic rehabilitation tool in patients with metabolic diseases, such as obesity and diabetes.

PMID:33202347 | DOI:10.1016/j.tice.2020.101456

Comput Struct Biotechnol J. 2020 Sep 20;18:2596-2609. doi: 10.1016/j.csbj.2020.09.026. eCollection 2020.

ABSTRACT

PURPOSE: Visceral fat is an independent risk factor for metabolic and cardiovascular disease. The study aimed to investigate the associations between gut microbiome and visceral fat.

METHODS: We recruited 32 obese adults and 30 healthy controls at baseline. Among the obese subjects, 14 subjects underwent laparoscopic sleeve gastrectomy (LSG) and were followed 6 months after surgery. Abdominal visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by magnetic resonance imaging. Waist, hipline, waist-to-hip ratio (WHR) and body mass index (BMI) were included as simple obese parameters. Gut microbiome was analyzed by metagenomic sequencing.

RESULTS: Among the obese parameters, VFA had the largest number of correlations with the species that were differentially enriched between obese and healthy subjects, following by waist, WHR, BMI, hipline, and SFA. Within the species negatively correlated with VFA, Eubacterium eligens had the strongest correlation, following by Clostridium citroniae, C. symbiosum, Bacteroides uniformis, E. ventriosum, Ruminococcaceae bacterium D16, C. hathewayi, etc. C. hathewayi and C. citroniae were increased after LSG. Functional analyses showed that among all the obese parameters, VFA had strongest correlation coefficients with the obesity-related microbial pathways. Microbial pathways involved in carbohydrate fermentation and biosynthesis of L-glutamate and L-glutamine might contribute to visceral fat accumulation.

CONCLUSIONS: Visceral fat was more closely correlated with gut microbiome compared with subcutaneous fat, suggesting an intrinsic connection between gut microbiome and metabolic cardiovascular diseases. Specific microbial species and pathways which were closely associated with visceral fat accumulation might contribute to new targeted therapies for metabolic disorders.

PMID:33033580 | PMC:PMC7528071 | DOI:10.1016/j.csbj.2020.09.026

BMC Endocr Disord. 2020 Oct 7;20(1):152. doi: 10.1186/s12902-020-00617-1.

ABSTRACT

BACKGROUND: Metabolic inflammation is an essential event in obesity-induced diabetes and insulin resistance. In obesity, an increasing number of macrophages recruited into visceral adipose tissues undergo significant M₁-like polarization, secreting variable amounts of pro-inflammatory cytokines and causing insulin resistance. Piperine has excellent anti-inflammatory activities and may be used in the treatment of a variety of inflammatory diseases. In this study, we investigated the effect of piperine on adipose tissue inflammation and insulin resistance in obese mice.

METHODS: Newborn mice were subcutaneously (s.c.) injected with monosodium glutamate (MSG) to establish a diabetes model. After 24 weeks, the MSG obese mice were divided into three groups and treated with piperine (40 mg/kg/day), metformin (150 mg/kg/day) and vehicle for 10 successive weeks, respectively.

RESULTS: The obesity model was successfully established, as the body weight, insulin resistance, fasting blood glucose (FBG) and dyslipidemia were significantly increased. The 10-week administration of piperine to the obese mice not only significantly decreased the elevated FBG (Model: 6.45 ± 0.41 mM; Piperine: 4.72 ± 0.44 mM, p < 0.01), serum TC (Model: 5.66 ± 0.66 mM; Piperine: 3.55 ± 0.30 mM, p < 0.01) and TG (Model: 1.41 ± 0.08 mM; Piperine: 0.94 ± 0.05 mM, p < 0.001), but also enhanced the glucose infusion rate in the hyperglycemic clamp experiment. Meanwhile, piperine improved glucose intolerance and insulin resistance in MSG obese mice. Piperine markedly decreased the total and differential white blood cell (WBC) count, the serum levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines such as galectin-3 (Gal-3) and interleukin-1β (IL-1β). Furthermore, piperine clearly down-regulated the mRNA levels of pro-inflammatory cytokines and the protein levels of M₁-like polarization marker CD11c and Gal-3 in adipose tissues. The in vitro study showed that piperine inhibited LPS-stimulated polarization of RAW 264.7 cells toward the M₁ phenotype.

CONCLUSIONS: Piperine served as an immunomodulator for the treatment of obesity-related diabetes through its anti-inflammatory effects, which might be achieved by inhibiting macrophages M₁ polarization in adipose tissues.

PMID:33028294 | PMC:PMC7542877 | DOI:10.1186/s12902-020-00617-1

Neurosci Res. 2021 Sep;170:201-207. doi: 10.1016/j.neures.2020.08.005. Epub 2020 Sep 17.

ABSTRACT

Obesity is a growing worldwide public health issue and is associated with a range of comorbidities, including cognitive deficits. The present study investigated synaptic changes in the hippocampus during the development of obesity. The treatment of newborn mice with monosodium-L-glutamate (MSG, 2 mg/g) induced obesity and recognition memory deficits in the novel object recognition (NOR) test at 16-17 weeks, but not at 8-9 weeks. Hippocampal synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), and excitatory synaptic transmission at Schaffer collateral-CA1 (SC-CA1) synapses were compared between MSG-treated mice and age-matched control mice. LTP and fiber volley amplitudes were enhanced in MSG-treated mice at 16-17 weeks, but not at 8-9 weeks. Furthermore, the strength of paired-pulse facilitation (PPF) changed in MSG-treated mice at 16-17 weeks, but not at 8-9 weeks. These results suggest that enhanced LTP in the SC-CA1 synapses of MSG-induced obese mice involves presynaptic rather than postsynaptic mechanisms.

PMID:32949668 | DOI:10.1016/j.neures.2020.08.005

Obes Res Clin Pract. 2020 Sep-Oct;14(5):479-486. doi: 10.1016/j.orcp.2020.07.009. Epub 2020 Aug 29.

ABSTRACT

We evaluated the effects of splenectomy on glucose homeostasis in obese and non-obese rats. Obesity was induced by subcutaneous injections of monosodium glutamate (MSG; 4g/kg) in neonatal rats. Control (non-obese) animals received equimolar saline. Splenectomy (SPL) was performed at 21 or 60 days of life (SPL₂₁ and SPL₆₀) in MSG obese and non-obese groups. Glucose tolerance, insulin resistance (IR), adiposity, histology of white adipose tissue (WAT) depots and glucose-induced insulin secretion (GIIS) in isolated pancreatic islets were evaluated at 90 days of life. In non-obese, despite of hyperphagia, the spleen ablation reduced body weight gain and energy efficiency, without changes in GIIS or IR. Slight reduction in glucose tolerance and augmented adipocyte size in subcutaneous WAT was noted in non-obese SPL₂₁ group. In MSG-SPL₂₁ rats was observed augmented body weight gain and energy efficiency, without alter adipocyte size. In contrast, MSG-SPL₆₀ rats had lower body weight gain, reduced energy efficiency and smaller adipocyte size in WAT visceral depot in relation to MSG non-operated. Spleen ablation reduced insulin plasma levels in the MSG-SPL₂₁ and MSG-SPL₆₀ groups. Moreover, splenectomy reduced GIIS and improved glucose tolerance in MSG-SPL₂₁ group. In MSG-SPL₆₀ rats were observed reduction in IR, without changes in GIIS, despite of elevated glucokinase expression in pancreatic islets. In conclusion, spleen ablation reduces body weight in non-obese rats and slightly modifies glucose homeostasis. In contrast, in MSG-induced obesity, absence of the spleen can ameliorate glucose tolerance and reduce insulin secretion, improving insulin sensitivity.

PMID:32868251 | DOI:10.1016/j.orcp.2020.07.009

Curr Cancer Drug Targets. 2020;20(11):868-874. doi: 10.2174/1568009620999200730184514.

ABSTRACT

BACKGROUND: Obesity is a significant risk factor for the development of types of cancer. Programmed death 1 and its ligand programmed death-ligand 1 (PD-L1) play a crucial role in tumor immune escape. Although, the role of PD-L1 in obesity-associated hepatocellular carcinoma (HCC) remains unknown. We previously showed that the natural flavonoid pentamethylquercetin (PMQ) possesses anti-obesity properties.

OBJECTIVE: This study was designed to investigate the effects of PMQ on the development of HCC in obese mice and whether PMQ regulates PD-L1 and expression in HCC.

METHODS: Monosodium glutamate-induced obese mice were inoculated with H22 tumor cells. Tumor volumes and weights were measured. In vitro, 3T3-L1 preadipocytes were differentiated and lipid accumulation was measured by oil-red staining, and IFN-γ level was detected by Elisa. Hepatoma HepG2 cells were treated with conditional media from 3T3-L1 adipocytes (adi-CM). Western blotting was applied to detect PD-L1 protein levels in tumor tissue and HepG2 cells.

RESULTS: Compared with control mice, H22 tumors grew faster and exhibited higher PD-L1 protein levels in obese mice. PMQ inhibited H22 tumor growth and reduced PD-L1 expression in tumor tissues. PD-L1 protein level was elevated in adi-CM-treated HepG2 cells. IFN-γ was detectable in adi-CM and exogenous IFN-γ induced PD-L1 expression in HepG2 cells. PMQ affected the differentiation of 3T3-L1 preadipocytes, decreased the level of IFN-γ secreted by adipocytes and downregulated adi-CM-induced PD-L1 expression in HepG2 cells.

CONCLUSION: PMQ could inhibit HCC progression in obese mice at least in part through down-regulating adipocytes-induced PD-L1 expression via IFN-γ signaling.

PMID:32748749 | DOI:10.2174/1568009620999200730184514

Arq Bras Cir Dig. 2020 Jul 8;33(1):e1497. doi: 10.1590/0102-672020190001e1497.

ABSTRACT

BACKGROUND: Effects of duodenal-jejunal bypass surgery (DJB) on the proliferation of nuclei and the area of adipocytes in the brown adipose tissue of obese rats. Thermogenic activity in the brown adipose tissue (BAT) of obese individuals is reduced, and this condition may be modified by bariatric surgery (BS).

AIM: To characterize fat deposition in BAT from hypothalamic obese (HyO) rats submitted to duodenal-jejunal-bypass (DJB) surgery.

METHODS: For induction of hypothalamic obesity, newborn male Wistar rats were treated with subcutaneous injections of monosodium glutamate (MSG). The control (CTL) group received saline solution. At 90 days, the HyO rats were submitted to DJB or sham operation, generating the HyO-DJB and HyO-SHAM groups. At 270 days, the rats were euthanized, and the BAT was weighed and submitted to histological analysis.

RESULTS: Compared to BAT from CTL animals, the BAT from HyO-SHAM rats displayed increased weight, hypertrophy with greater lipid accumulation and a reduction in nucleus number. DJB effectively increased nucleus number and normalized lipid deposition in the BAT of HyO-SHAM rats, similar to that observed in CTL animals.

CONCLUSION: DJB surgery avoided excessive lipid deposition in the BAT of hypothalamic obese rats, suggesting that this procedure could reactivate thermogenesis in BAT, and contribute to increase energy expenditure.

PMID:32667527 | PMC:PMC7357552 | DOI:10.1590/0102-672020190001e1497

J Diabetes Metab Disord. 2020 Feb 16;19(1):289-296. doi: 10.1007/s40200-020-00506-3. eCollection 2020 Jun.

ABSTRACT

BACKGROUND AND AIMS: сomparative animal study of effectiveness of intermittent administration of lyophilized single-, three- and alive multistrain probiotic in short courses on insulin resistance (IR) in rats with experimental obesity.

METHODS: 70 rats were divided into 7 groups (n = 10 in each). Rats of group I were left intact. Newborn rats in groups II-VII were administered monosodium glutamate (MSG) (4 mg/g) by injection. Rats in group II (MSG-obesity group) were left untreated. The rats in groups III-V received lyophilized mono-probiotics B.animalis VKL, B.animalis VKB, L.casei IMVB-7280 respectively. The rats in group VI received all three of these probiotic strains mixed together. Group VII was treated with multi-probiotic "Symbiter", containing 14 different live probiotic strains (Lactobacillus, Bifidobacterium, Propionibacterium, Acetobacter genera).

RESULTS: Treatment of newborn rats with MSG lead to the development of obesity in all MSG-obesity rats and up to 20-70% after probiotic administration. Additions to probiotic composition, with preference to alive strains (group VII), led to significantly lower rates of obesity, decrease in HOMA-IR (p < 0.001), proinflammatory cytokines levels - IL-1β (p = 0.003), IL-12Bp40 (p < 0.001) and elevation of adiponectin (p = 0.003), TGF-β (p = 0.010) in comparison with MSG-obesity group. Analysis of results in groups treated with single-strain probiotics (groups III-V) shows significant decrease in HOMA-IR, but changes were less pronounced as compared to mixture groups and did not achieve intact rats level. Other metabolic parameters were not affected significantly by single strains.

CONCLUSION: Our findings provide major clues for how to design and use probiotics with more efficient compositions in obesity and IR management and may bring new insights into how host-microbe interactions contribute to such protective effects.

PMID:32550178 | PMC:PMC7270447 | DOI:10.1007/s40200-020-00506-3

Iran J Basic Med Sci. 2020 Apr;23(4):416-430. doi: 10.22038/IJBMS.2020.43060.10123.

ABSTRACT

Monosodium glutamate is a sodium salt of a nonessential amino acid, L-glutamic acid, which is widely used in food industry. Glutamate plays an important role in principal brain functions including formation and stabilization of synapses, memory, cognition, learning, as well as cellular metabolism. However, ingestion of foodstuffs rich in monosodium glutamate can result in the outbreak of several health disorders such as neurotoxicity, hepatotoxicity, obesity and diabetes. The usage of medicinal plants and their natural products as a therapy against MSG used in food industry has been suggested to be protective. Calendula officinalis, Curcuma longa, Green Tea, Ginkgo biloba and vitamins are some of the main natural products with protective effect against mentioned monosodium glutamate toxicity through different mechanisms. This review provides a summary on the toxicity of monosodium glutamate and the protective effects of natural products against monosodium glutamate -induced toxicity.

PMID:32489556 | PMC:PMC7239414 | DOI:10.22038/IJBMS.2020.43060.10123

Cancer Cell Int. 2020 May 20;20:179. doi: 10.1186/s12935-020-01269-w. eCollection 2020.

ABSTRACT

BACKGROUND: Obesity confers increased risk for various types of cancer. PD-L1 is a key molecule in tumor immune evasion by inducing T cell exhaustion. The relationship between obesity and PD-L1 is still ambiguous. This study was designed to reveal the development of hepatocellular carcinoma and melanoma in obese mice and to investigate if adipocytes regulate PD-L1 expression and the underlying mechanism.

METHODS: Monosodium glutamate-induced obese mice were inoculated with H22 tumor cells and High fat diet (HFD)-induced obese mice were inoculated with B16-F1 mouse melanoma cells. Human hepatoma HepG2 cells and B16-F1 cells were treated with conditional media from 3T3-L1 adipocytes (adi-CM). Neutralized anti-TNF-α and anti-IL-6 antibodies and inhibitor of NF-κB or STAT3 were used to reveal the mechanism of effect of adi-CM.

RESULTS: In obese mice, H22 and B16-F1 tumor tissues grew faster and PD-L1 expression in tumor tissue was increased. Adi-CM up-regulated PD-L1 level in HepG2 and B16-F1 cells in vitro. Differentiated 3T3-L1 adipocytes secreted TNF-α and IL-6, and neutralizing TNF-α and/or IL-6 reduced PD-L1 expression in adi-CM-treated cells. p-NF-κB/NF-κB level was downregulated in HepG2 and B16-F1 cells, and p-STAT3/STAT3 level was also decreased in HepG2 cells. In addition, inhibitor of NF-κB or STAT3 reversed the effect of adi-CM on PD-L1 expression.

CONCLUSIONS: TNF-α and IL-6 secreted by adipocytes up-regulates PD-L1 in hepatoma and B16-F1 cells, which may be at least partially involved in the role of obesity in promoting tumor progression.

PMID:32477009 | PMC:PMC7240984 | DOI:10.1186/s12935-020-01269-w

J Ethnopharmacol. 2020 Oct 5;260:112972. doi: 10.1016/j.jep.2020.112972. Epub 2020 May 22.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Fagara tessmannii is a shrub of the African rainforests in South-West, Centre, South and East provinces in Cameroon. It is used in traditional medicine for the treatment of tumors, swellings, inflammation, gonorrhoea, schistosomiasis, antifungal, heart diseases and as anti-hypertensive.

AIM OF THE STUDY: We investigated the potential effects of F. tessmannii on cardiovascular risk related to monosodium glutamate-induced obesity.

MATERIALS AND METHODS: Monosodium glutamate (MSG, 4 mg/g/day) was injected subcutaneously to newborn Wistar rats for the four consecutive first days of their life and on the 6th, 8th and 10th day after birth. After 21 weeks, obese rats were treated orally with F. tessmannii (100 or 200 mg/kg/day), orlistat (10 mg/kg/day) or telmisartan (10 mg/kg/day) for 6 weeks. Body weight, obesity, body mass index (BMI), Lee index, insulin sensitivity and glucose tolerance, blood pressure, lipid profile as a Coronary Risk Index (CRI), and reactivity of isolated thoracic aorta were evaluated.

RESULTS: In addition to significantly decrease body weight (17.60% and 20.34%), BMI, Lee's index, retroperitoneal fat, total adiposity, and coronary risk indicators, F. tessmannii has significantly decreased insulin resistance and hyperglycemia and high blood pressure observed in MSG-obese rats. The high contractility to phenylephrine as well as the hypersensitivity to sodium nitroprusside (a nitric oxide-donor), observed in MSG aortic rings were significantly reduced by the F. tessmannii extract. Enhanced serum Na⁺ and Cl^- levels and decreased K⁺ observed in obese rats were also significantly reversed after F. tessmannii treatment.

CONCLUSIONS: F. tessmannii fights against obesity and associated cardiovascular risks by modulating production and vascular responsiveness to vasoactive factors, monitoring premature aging. F. tessmannii promotes the loss of ectopic fat and other fatty tissues, the sensitivity of the peripherical tissues to insulin, the energy expenditure and the renovascular decompression and regulates ions movement which prevents hypertension.

PMID:32446928 | DOI:10.1016/j.jep.2020.112972

J Trace Elem Med Biol. 2020 Sep;61:126508. doi: 10.1016/j.jtemb.2020.126508. Epub 2020 Apr 12.

ABSTRACT

BACKGROUND: Vanadium (V) is an element with a wide range of effects on the mammalian organism. The ability of this metal to form organometallic compounds has contributed to the increase in the number of studies on the multidirectional biological activity of its various organic complexes in view of their application in medicine.

OBJECTIVE: This review aims at summarizing the current state of knowledge of the pharmacological potential of V and the mechanisms underlying its anti-viral, anti-bacterial, anti-parasitic, anti-fungal, anti-cancer, anti-diabetic, anti-hypercholesterolemic, cardioprotective, and neuroprotective activity as well as the mechanisms of appetite regulation related to the possibility of using this element in the treatment of obesity. The toxicological potential of V and the mechanisms of its toxic action, which have not been sufficiently recognized yet, as well as key information about the essentiality of this metal, its physiological role, and metabolism with certain aspects on the timeline is collected as well. The report also aims to review the use of V in the implantology and industrial sectors emphasizing the human health hazard as well as collect data on the directions of further research on V and its interactions with Mg along with their character.

RESULTS AND CONCLUSIONS: Multidirectional studies on V have shown that further analyses are still required for this element to be used as a metallodrug in the fight against certain life-threatening diseases. Studies on interactions of V with Mg, which showed that both elements are able to modulate the response in an interactive manner are needed as well, as the results of such investigations may help not only in recognizing new markers of V toxicity and clarify the underlying interactive mechanism between them, thus improving the medical application of the metals against modern-age diseases, but also they may help in development of principles of effective protection of humans against environmental/occupational V exposure.

PMID:32305626 | PMC:PMC7152879 | DOI:10.1016/j.jtemb.2020.126508

Curr Pharm Biotechnol. 2020;21(11):1099-1106. doi: 10.2174/1389201021666200318124922.

ABSTRACT

BACKGROUND: Chlorogenic Acid (CA) has diverse, recognized health effects.

OBJECTIVE: This study aimed to explore the effects of CA on fat reduction and the underlying mechanism of these effects.

MATERIALS AND METHODS: First, we established a Monosodium Glutamate (MSG)-induced obesity mouse model and subjected the mice to 4 weeks of CA gavage. Then, we established an oleic acidinduced model of human fatty liver in HepG2 cells, and administered a CA intervention to the cells for 48 h. Finally, we used Oil red O staining, biochemical detection kits, RT-PCR and Western blot analysis to evaluate the effects of CA on fat reduction and on related pathways.

RESULTS: The CA treatment could reduce fat accumulation in the liver and reduce blood lipid levels. In addition, CA decreased the mRNA and protein levels of peroxisome proliferator-activated receptor gamma, coactivator 1 α (PGC-1α) and Uncoupling Protein 1 (UCP1) in the MSG-induced obesity mouse model and the oleic acid-induced HepG2 cells.

CONCLUSION: Based on the above results, we deduced that CA could reduce body weight and fat deposition in vitro and in vivo and that the mechanism may be related to the PGC-1α/UCP-1 pathway. CA can be developed as a drug to lower blood lipids and to treat obesity.

PMID:32188382 | DOI:10.2174/1389201021666200318124922

Endocrine. 2020 Jul;69(1):18-29. doi: 10.1007/s12020-020-02256-x. Epub 2020 Mar 14.

ABSTRACT

Diabetes is one of the most common metabolic diseases. Aside from the genetic factor, previous studies stated that other factors such as environment, lifestyle, and paternal-maternal condition play critical roles in diabetes through DNA methylation in specific areas of the genome. One of diabetic cases is caused by insulin resistance and changing the homeostasis of blood glucose control so glucose concentration stood beyond normal rate (hyperglycemia). High fat diet has been frequently studied and linked to triggering diabetes. However, most Asians consume rice (or food with high carbohydrate) and food with monosodium glutamate (MSG). This habit could lead to pathophysiology of type 2 diabetes mellitus (T2D). Previous studies showed that high-carbohydrate or high-MSG diet could change gene expression or modify protein activity in body metabolism. This imbalanced metabolism can lead to pleiotropic effects of diabetes mellitus. In this study, the authors have attempted to relate various changes in genes expression or protein activity to the high-carbohydrate and high-MSG-induced diabetes. The authors have also tried to relate several genes that contribute to pathophysiology of T2D and proposed several ideas of genes as markers and target for curing people with T2D. These are done by investigating altered activities of various genes that cause or are caused by diabetes. These genes are selected based on their roles in pathophysiology of T2D.

PMID:32172486 | DOI:10.1007/s12020-020-02256-x

BMC Gastroenterol. 2020 Feb 27;20(1):46. doi: 10.1186/s12876-020-01194-2.

ABSTRACT

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Within the spectrum of NAFLD, non-alcoholic steatohepatitis (NASH) in combination with hepatic inflammation and fibrosis can lead to liver cirrhosis and hepatocellular carcinoma. Dysbiosis was reported to contribute to NASH pathogenesis. This study aimed to determine the effects of fructo-oligosaccharides (FOS) on steatohepatitis and visceral adiposity in an obese mouse model of NASH.

METHODS: Twelve newborn C57BL/6 J male mice were subcutaneously injected with monosodium glutamate (MSG) to induce obesity on a conventional diet. Six mice were also administered 5% FOS via drinking water from 10 weeks of age. At 18 weeks, histological characteristics of the liver and epididymal fat were compared between the groups. Hepatic mRNA expression of lipid metabolism enzymes and SCFA in feces and sera were measured.

RESULTS: Hepatic steatosis, inflammatory cell infiltration, and hepatocyte ballooning in the liver and increased hepatic mRNA expression of fatty acid synthase and glycerol-3-phosphate acyltransferase were observed in the MSG-treated mice. FOS treatment improved the liver pathology and blunted the increases in the mRNA expression levels of lipid metabolism enzymes. In addition, FOS inhibited adipocyte enlargement and formation of crown-like structures and reduced the M1 macrophage frequency in the epididymal fat of the MSG mice (39.4% ± 3.0% vs. 22.8% ± 0.7%; P = 0.001). FOS increased not only the fecal concentrations of n-butyric acid (0.04 ± 0.01 vs. 0.38 ± 0.14 mg/g, P = 0.02), propionic acid (0.09 ± 0.03 vs. 0.42 ± 0.16 mg/g, P = 0.02), and acetic acid (0.65 ± 0.16 vs. 1.48 ± 0.29 mg/g, P = 0.03) but also the serum concentration of propionic acid (3.9 ± 0.5 vs. 8.2 ± 0.5 μmol/L, P = 0.001).

CONCLUSIONS: FOS ameliorates steatohepatitis, visceral adiposity, and chronic inflammation by increasing SCFA production.

PMID:32103741 | PMC:PMC7045471 | DOI:10.1186/s12876-020-01194-2

Biomed Res Int. 2020 Jan 30;2020:3243906. doi: 10.1155/2020/3243906. eCollection 2020.

ABSTRACT

OBJECTIVE: Obesity causes a variety of metabolic alterations that may contribute to abnormalities of the cardiac structure and function (obesity cardiomyopathy). In previous works, we have shown that pentamethylquercetin (PMQ) significantly improved metabolic disorders in obese mice and it inhibited pressure overload-induced cardiac remodeling in mice. However, its potential benefit in obesity cardiomyopathy remains unclear. The aim of this study was to investigate the effects of PMQ on cardiac remodeling in obese mice.

METHODS: We generated a monosodium glutamate-induced obese (MSG-IO) model in mice, which were treated with PMQ (5, 10, and 20 mg/kg) for 16 weeks consecutively. We examined the metabolic parameters and observed cardiac remodeling by performing cardiac echocardiography and Masson's staining. The expression levels of molecules associated with the endogenous antioxidant system, including the sestrins/kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway, were analyzed by western blotting and immunofluorescent staining.

RESULTS: We found that PMQ treatment significantly ameliorated obesity phenotypes and improved metabolic disorders in MSG-IO mice. PMQ decreased the heart wall thickness and attenuated cardiac fibrosis. Further study revealed that the protective effects of PMQ might be mediated by promoting Keap1 degradation and augmenting sestrins expression and Nrf2 nuclear translocation.

CONCLUSION: Our findings indicated that PMQ ameliorated cardiac remodeling in obese mice by targeting the sestrins/Keap1/Nrf2 signaling pathway.

PMID:32090078 | PMC:PMC7013309 | DOI:10.1155/2020/3243906

Nat Rev Gastroenterol Hepatol. 2020 Jun;17(6):352-364. doi: 10.1038/s41575-019-0253-4. Epub 2020 Feb 21.

ABSTRACT

Over the past several decades, the incidence of early-onset colorectal cancer (EOCRC; in patients <50 years old) has increased at an alarming rate. Although robust and scientifically rigorous epidemiological studies have sifted out environmental elements linked to EOCRC, our knowledge of the causes and mechanisms of this disease is far from complete. Here, we highlight potential risk factors and putative mechanisms that drive EOCRC and suggest likely areas for fruitful research. In addition, we identify inconsistencies in the evidence implicating a strong effect of increased adiposity and suggest that certain behaviours (such as diet and stress) might place nonobese and otherwise healthy people at risk of this disease. Key risk factors are reviewed, including the global westernization of diets (usually involving a high intake of red and processed meats, high-fructose corn syrup and unhealthy cooking methods), stress, antibiotics, synthetic food dyes, monosodium glutamate, titanium dioxide, and physical inactivity and/or sedentary behaviour. The gut microbiota is probably at the crossroads of these risk factors and EOCRC. The time course of the disease and the fact that relevant exposures probably occur in childhood raise important methodological issues that are also discussed.

PMID:32086499 | DOI:10.1038/s41575-019-0253-4

Biomed Pharmacother. 2020 Apr;124:109879. doi: 10.1016/j.biopha.2020.109879. Epub 2020 Jan 25.

ABSTRACT

AIMS: African walnuts were previously shown to modulate hepatic lipid bio-accumulation in obesity. Herein, we investigated the impact of the nuts on fat accumulation in adipose and ectopic regions, and associated oxidatiive stress status in obese rats.

MATERIALS AND METHODS: Whole ethanol extract (WE) of the nuts, and its liquid-liquid fractions-ethyl acetate (ET) and residue (RES) were separately administered to obese rats for 6 weeks. The normal (NC) and obese (OC) controls received normal saline and the standard control (SC), orlistat (5.14 mg/kg b.w.), during the same period. Thereafter, the animals were euthanized and the adipose, brain, kidneys and heart tissues were studied.

RESULTS: The change in body weight to naso-anal length which increased by 63.52 % in OC compared to NC (p < 0.05), decreased by 57.88, 85.80 and 70.20 % in WE, ET and RES-treated groups, respectively, relative to the OC (p < 0.05). Also, adipose tissue weights were lowered upon treatment with the extracts and fractions versus OC (p < 0.05). Total lipids, phospholipids, triacylglycerol and cholesterol concentrations in the studied tissues which were higher in OC (p < 0.05) were lowered (p < 0.05) and compared favorably with SC. Further, malondialdehyde levels in the tissues were lowered upon treatment, compared to the OC (p < 0.05). Glutathione level and activities of glutathione peroxidase, superoxide dismutase and glutathione-S-transferase which were decreased (p < 0.05) in OC, were restored upon treatment with the extracts, relative to the obese control (p < 0.05).

SIGNIFICANCE: African walnuts assuaged lipogenesis, oxidative stress and peroxidation in extra-hepatic tissues of obese rats, hence, may attenuate ectopic fat accumulation and its associated pathogenesis.

PMID:31991383 | DOI:10.1016/j.biopha.2020.109879

Cell Biol Int. 2020 Mar;44(3):744-754. doi: 10.1002/cbin.11269. Epub 2019 Dec 4.

ABSTRACT

Recent epidemiologic studies pointed out a significant correlation between dietary monosodium glutamate (MSG) and increased body mass index. Corroborating evidences came from animal studies depicting a clear association between dietary MSG intake and increased abdominal fat, dyslipidemia, adipocyte hypertrophy, and total body weight gain. Taken together with the inferred absence of conspicuous hypothalamic neuropathies the hallmark of disease etiopathogenesis in MSG-obese animals, these animal studies with dietary MSG strongly argue for the presence of an alternative non-neuronal route for MSG to mediate its adipose tissue-specific phenotype and body weight gain. On the basis of this hypothesis, we investigated the direct effect of physiologically relevant low (100 µM), moderate (250 µM), and high dosages (2.5 and 25 mM) of MSG on distinct phases of adipocyte differentiation. MSG-dependent changes in cell proliferation and lipid accumulation were analyzed by cell proliferation assays, flow cytometry, and biochemical methods, respectively. Physiologically relevant high dosages MSG demonstrated a significant potential in reducing MCE and thereof adipogenic capacity of preadipocytes in a dose-dependent manner by restricting the availability of critical mitogenic proteins, CCAAT/enhancer-binding protein β (CEBPβ), and the mitotic cyclin B. Our findings warrant further investigations to unravel the effect of long-term dietary MSG intake on capacity of preadipocytes in different fat depots to undergo mitotic clonal expansion and hyperplasia in rodent models and human subjects, respectively.

PMID:31769558 | DOI:10.1002/cbin.11269

Int J Mol Sci. 2019 Oct 30;20(21):5414. doi: 10.3390/ijms20215414.

ABSTRACT

In clinical practice, the metabolic syndrome (MetS) is often associated with chronic obstructive pulmonary disease (COPD). Although gender differences in MetS are well documented, little is known about sex-specific differences in the pathogenesis of COPD, especially when combined with MetS. Consequently, it is not clear whether the same treatment regime has comparable efficacy in men and women diagnosed with MetS and COPD. In the present study, using sodium glutamate, lipopolysaccharide, and cigarette smoke extract, we simulated lipid metabolism disorders, obesity, hyperglycemia, and pulmonary emphysema (comorbidity) in male and female C57BL/6 mice. We assessed the gender-specific impact of lipid metabolism disorders and pulmonary emphysema on angiogenic precursor cells (endothelial progenitor cells (EPC), pericytes, vascular smooth muscle cells, cells of the lumen of the nascent vessel), as well as the biological effects of pegylated glucagon-like peptide 1 (pegGLP-1) in this experimental paradigm. Simulation of MetS/COPD comorbidity caused an accumulation of EPC (CD45^-CD31⁺CD34⁺), pericytes, and vascular smooth muscle cells in the lungs of female mice. In contrast, the number of cells involved in the angiogenesis decreased in the lungs of male animals. PegGLP-1 had a positive effect on lipids and area under the curve (AUC), obesity, and prevented the development of pulmonary emphysema. The severity of these effects was stronger in males than in females. Furthermore, PegGLP-1 stimulated regeneration of pulmonary endothelium. At the same time, PegGLP-1 administration caused a mobilization of EPC (CD45^-CD31⁺CD34⁺) into the bloodstream in females and migration of precursors of angiogenesis and vascular smooth muscle cells to the lungs in male animals. Gender differences in stimulatory action of pegGLP-1 on CD31⁺ endothelial lung cells in vitro were not observed. Based on these findings, we postulated that the cellular mechanism of in vivo regeneration of lung epithelium was at least partly gender-specific. Thus, we concluded that a pegGLP-1-based treatment regime for metabolic disorder and COPD should be further developed primarily for male patients.

PMID:31671663 | PMC:PMC6862381 | DOI:10.3390/ijms20215414

Clin Exp Pharmacol Physiol. 2020 Feb;47(2):286-293. doi: 10.1111/1440-1681.13197. Epub 2019 Nov 12.

ABSTRACT

Here, we investigate the effects of exercise training on glucose- and cholinergic-induced insulin secretion in pancreatic islets from obese and lean rats. Male Wistar rats were treated with monosodium glutamate (MSG) for the first 5 days of life, while control (CON) rats received saline. At 21 days, the rats were divided into exercised (EXE) and sedentary (SED) groups. The EXE rats swam for 30 minutes, three times/week, for 10 weeks. After this, MSG-SED rats showed hyperglycaemia, hypertriglyceridaemia and hyperinsulinaemia. Besides, islets from MSG-SED rats exhibited increased glucose-stimulated insulin secretion (GSIS), followed by impaired glucose sensitivity, absence of glucose-amplifying pathway and weak cholinergic response. In contrast, adiposity, hyperinsulinaemia and hypertriglyceridaemia were reduced in MSG-EXE rats. Moreover, islets from MSG-EXE rats exhibited lower GSIS and improved islet glucose sensitivity, without restoration of the glucose-amplifying pathway or alteration in the weak cholinergic effect of these islets. In islets from CON-EXE rats we also observed reduced GSIS and absence of glucose-amplifying effects and an accentuated reduction in cholinergic insulinotropic responses, without effect on glucose sensitivity in pancreatic islets from this group. Neither obesity nor exercise modified Muscarinic Receptor 3 (M3R) immunocontent or its downstream pathways (PKC and PKA). Moreover, only CON-EXE showed increased GSIS in the presence of calcium blocker, Thapsigargin. In conclusion, swimming training reduces GSIS and cholinergic responsiveness in isolated pancreatic islets from lean and hypothalamic obese rats, which could be due to the inhibition of glucose-amplifying pathways.

PMID:31630415 | DOI:10.1111/1440-1681.13197

Front Neurosci. 2019 Sep 12;13:968. doi: 10.3389/fnins.2019.00968. eCollection 2019.

ABSTRACT

INTRODUCTION: Free glutamate is a common dietary flavor enhancer and is also an important excitatory neurotransmitter in the body. A good number of food additives which contain glutamate are found in the Western Diet, and this diet has also been linked to increased risk of cognitive dysfunction.

OBJECTIVE: To examine the effects of dietary glutamate on hippocampal and non-hippocampal memory performance, and whether consuming a diet high in fat/sugar could influence any observed associations.

METHODS: Sixty-four adult male Sprague-Dawley rats were trained concurrently on two different discrimination problems: (1) Pavlovian serial feature negative (sFN) discrimination, in which a brief tone stimulus was reinforced with sucrose pellets when it was presented alone (T+ trials) and non-reinforced on trials when it was preceded by the presentation of a brief light (LT- trials); and (2) a simple discrimination (SD) problem in which a white noise (WN+) cue was reinforced with sucrose pellets and a clicker (C-) stimulus was not reinforced. Previous research has shown that sFN, but not SD performance, depends on the functional integrity of the hippocampus. After solving both problems, the rats were assigned to one of four ad libitum-fed diet groups, matched on weight and discrimination performance: (1) high fat, high sugar western-style diet (WD), (2) standard laboratory rodent chow diet (chow), (3) WD + monosodium glutamate (MSG), or (4) chow + MSG.

RESULTS: After 14 weeks, rats fed WD had higher adiposity than rats fed chow. Consistent with previous findings, rats fed WD exhibited impaired performance on the sFN problem, but not on the SD, relative to rats fed chow. Adding MSG to WD abolished this impairment, whereas rats fed chow + MSG had impaired sFN performance compared to rats fed chow alone. No differences in performance on the SD task were observed.

CONCLUSION: This study demonstrates differing effects of dietary glutamate on hippocampal dependent memory function, with MSG impairing hippocampal function in animals receiving chow, while improving hippocampal function in animals receiving a Western-type diet, high in fat and sugar. More research will be needed to explore the cause of these differential effects.

PMID:31572118 | PMC:PMC6751330 | DOI:10.3389/fnins.2019.00968

PLoS One. 2019 Aug 14;14(8):e0220720. doi: 10.1371/journal.pone.0220720. eCollection 2019.

ABSTRACT

Although monosodium glutamate (MSG)-induced neurotoxicity has been recognized for decades, the potential similarities of the MSG model to Alzheimer's disease (AD)-type neuropathology have only recently been investigated. MSG-treated mice were examined behaviourally and histologically in relation to some features of AD. Four-week old mice received 5 subcutaneous MSG (2 g/kg) injections on alternate days, or saline. At age 10-12 weeks, they were given a battery of behavioural tests for species-typical behaviours and working memory. The mice were killed at 12 weeks and the brains excised. Accumulation of hyperphosphorylated tau protein was assessed in cortical and hippocampal neurons by immunohistochemistry, and in cerebral cortical homogenates. A 78% increase in cortical concentrations of phosphorylated tau protein was observed in the MSG mice. Intracellular hyperphosphorylated tau immunostaining was observed diffusely in the cortex and hippocampus, together with cortical atrophic neurons, extensive vacuolation and dysmorphic neuropil suggestive of spongiform neurodegeneration. Nest-building was significantly impaired, and spontaneous T-maze alternation was reduced, suggesting defective short-term working memory. Subcutaneous MSG treatment also induced a 56% reduction in exploratory head dips in a holeboard (P = 0.009), and a non-significant tendency for decreased burrowing behaviour (P = 0.085). These effects occurred in the absence of MSG-induced obesity or gross locomotor deficits. The findings point to subcutaneous MSG administration in early life as a cause of tau pathology and compromised species-typical behaviour in rodents. Determining whether MSG can be useful in modelling AD requires further studies of longer duration and full behavioural characterization.

PMID:31412065 | PMC:PMC6693749 | DOI:10.1371/journal.pone.0220720

Food Nutr Res. 2019 Jul 17;63. doi: 10.29219/fnr.v63.1444. eCollection 2019.

ABSTRACT

BACKGROUND: Obesity and its related metabolic syndrome continue to be major public health problems. Monosodium L-glutamate (MSG) may cause metabolic diseases such as obesity. Meanwhile, the Chinese population has undergone rapid transition to a high-fat diet. There is little information available on the effect of MSG and fat alone, or in combination, on free fatty acids (FFAs), lipid metabolism and FFA receptors.

OBJECTIVE: The aim of this study was to evaluate the effects of MSG and fat alone, or in combination, on intestinal luminal FFAs and expression of gastrointestinal FFA receptors. The aim was also to test whether dietary fat and/or MSG could affect expression of genes related to fatty acid metabolism.

DESIGN: A total of 32 growing pigs were used and fed with four iso-nitrogenous and iso-caloric diets. Pigs in the four treatments received diets with one of two fat concentrations levels (4.4 and 9.4%) and one of two MSG dose levels (0 and 3%), in which most of the fat were brought by soybean oil. The concentration of short chain fatty acids (SCFAs) in cecum and colon, long chain fatty acids (LCFAs) in ileum, cecum and colon, and FFAs receptors expression in hypothalamus and gastrointestinal tract were determined.

RESULTS: MSG and/or fat changed intestinal luminal SCFAs, levels of LCFAs, and showed an antagonistic effect on most of LCFAs. Simultaneously, MSG and/or fat decreased the expression of FFA receptors in hypothalamus and gastrointestinal tract. MSG and/or fat promoted fat deposition through different ways in back fat.

CONCLUSION: Our results support that MSG and/or fat can alter intestinal luminal FFAs composition and concentration, especially LCFAs, in addition, the expression of FFA receptors in ileum and hypothalamus could be decreased. Moreover, MSG and/or fat can promote protein deposition in back fat, and affect the distribution and metabolism of fatty acids in the body tissues and the body's ability to perceive fatty acids; these results provide a reference for the occurrence of fat deposition and obesity caused by high-fat and monosodium glutamate diet.

PMID:31360149 | PMC:PMC6642617 | DOI:10.29219/fnr.v63.1444

Endocr Metab Immune Disord Drug Targets. 2020;20(3):365-379. doi: 10.2174/1871530319666190724114729.

ABSTRACT

BACKGROUND: Obesity is characterized by increased body fat and involves an imbalance between the synthesis and degradation of lipids.

OBJECTIVE: The study aimed to investigate the effect of African walnuts (Tetracarpidium conophorum) on lipids storage and the regulatory enzymes of hepatic lipid metabolism in obese rats.

METHODS: Nuts were extracted in ethanol (WE) and further separated to obtain the ethyl-acetate fraction (ET) and the residue (RES). These were administered orally to 3 groups of monosodium glutamate- obese rats (n = 6), respectively, for 6 weeks. Other groups in the study were: normal (NC), obese control (OC) and standard control (SC) which received orlistat. Hepatic total lipids, total phospholipids, triacylglycerol (TG), total cholesterol (TCHOL), 3-hydroxyl-3-methylglutaryl-CoA (HMG-CoA) reductase and paraoxonase were studied.

RESULTS: Total lipids, TG and TCHOL which increased in OC compared to NC group, decreased. HMG-CoA reductase activity decreased in the 3 study groups relative to OC. Paraoxonase activity which decreased in OC was up-regulated, while the magnitude of hepatic cholesterol decreased from 94.32 % in OC to 52.19, 65.43 and 47.04 % with WE, ET and RES, respectively. Flavonoids, alkaloids, glycosides, tannins and saponins were detected in the nut. GC-MS analysis revealed 16, 18 and 10 volatile components in WE, ET and RES, respectively. Unsaturated fatty acids (linolenic acids: 33.33, 47.95 and 50.93 %, and α-linolenic acids: 25, 19.66 and 26.63 %) in WE, ET and RES, respectively, are the most abundant, and likely to be responsible for the observed activity.

CONCLUSION: African walnuts can prevent hepatic lipid accumulation through reciprocal actions on HMG-CoA reductase and paraoxonase in obesity.

PMID:31339080 | DOI:10.2174/1871530319666190724114729

Appetite. 2019 Nov 1;142:104376. doi: 10.1016/j.appet.2019.104376. Epub 2019 Jul 18.

ABSTRACT

AIM: The neuropeptide neuromedin U (NMU) known for its role in appetite, feeding and energy balance could be involved in the control of food choice and taste sensitivity. We examined the association between NMU polymorphisms/haplotypes and taste thresholds and food preferences in a population of European children.

METHODS: A total of 578 subjects from the IDEFICS study (mean age 7.5 ± 0.8 SD, boys 53.6%) with NMU genotype data and food preference (salty, fatty, sweet, flavour and umami food) and taste threshold (salt, fat, sweet, umami) tests available were analysed. Three single nucleotide polymorphisms (SNPs; rs6827359, T:C; rs12500837, T:C; rs9999653, C:T) of NMU gene were analyzed and five major haplotypes were inferred. The associations between genotypes and food preferences or taste thresholds were investigated (odds ratios -OR, adjusted for age, sex and country). A p < 0.05 after false discovery rate adjustment (pFDR) was considered statistically significant.

RESULTS: The association between NMU genotypes and food preference showed two NMU SNPs associated with preference for food containing sodium glutamate (umami taste; rs6827359C, OR = 1.61, 95% confidence interval (CI):1.20-2.17; rs9999653T, OR = 1.59, 95%CI:1.18-2.13). In the haplotype analysis, the CTT haplotype showed an OR of 1.70 (95%CI:1.16-2.5) for the umami food preference, while CCT haplotype showed an OR of 1.63 (95%CI:1.11-2.40), compared to the most frequent haplotype (TTC). Carriers of CCT/CCT vs subjects with no CCT haplotype showed an OR of 4.78 (95%CI:1.86-12.30). Umami food preference was associated with low values of BMI z-score, arm circumferences, skinfolds and fat mass (pFDR<0.05). No association between NMU genetic variants and taste thresholds was found.

CONCLUSIONS: This study shows for the first time in children an association between preference for umami food and a NMU haplotype, previously found associated with low BMI values.

PMID:31326439 | DOI:10.1016/j.appet.2019.104376

Sci Rep. 2019 May 13;9(1):7287. doi: 10.1038/s41598-019-43017-9.

ABSTRACT

Post-translational modification (PTM) plays a critical role in increasing proteome complexity and diversifying protein functions. O-GlcNAc modification is a reversible, dynamic and highly abundant PTM catalyzed by a single pair of enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), regardless of substrates. The two enzymes are particularly enriched in the brain, and recent proteomic studies identified that a large number of neuron-specific proteins undergo O-GlcNAc modification. In addition, pathological conditions with aberrant O-GlcNAcylation such as diabetes and obesity are associated with the higher risk of cognitive decline and memory impairment. However, despite its prevalence in the brain, functional significance of O-GlcNAcylation in regulating neuronal properties remains unclear at the molecular level. Here, we report that an acute increase in O-GlcNAcylation induced by pharmacological inhibition of OGA significantly reduces the intrinsic excitability of hippocampal CA1 neurons through the cooperative modulation of multiple voltage-gated ion channels. Moreover, elevated O-GlcNAcylation also suppresses excitatory synaptic transmission at Schaffer collateral-CA1 synapses through the removal of GluA2-containing AMPA receptors from postsynaptic densities. Collectively, our findings demonstrate that a change in O-GlcNAcylation levels dynamically regulates hippocampal activity at both intrinsic and synaptic levels, providing a mechanistic link between dysregulated O-GlcNAcylation and hippocampal dysfunction.

PMID:31086206 | PMC:PMC6514166 | DOI:10.1038/s41598-019-43017-9

Life Sci. 2019 Jul 15;229:157-165. doi: 10.1016/j.lfs.2019.05.017. Epub 2019 May 8.

ABSTRACT

AIM: This study investigates the insulin sensitizer effect of carbenoxolone (CBX) and potentially involved peripheral mechanisms.

MAIN METHODS: Taking glucose transporter 4 (GLUT4) as a marker of glucose disposal, we investigated the CBX effects on whole-body insulin sensitivity and solute carrier 2a4 (Slc2a4)/GLUT4 expression in visceral (VAT) and subcutaneous (SAT) adipose tissues and soleus muscle of monosodium glutamate (MSG)-induced obese rats. Sterol regulatory element binding protein (SREBP1), an enhancer of Slc2a4 expression was analyzed through mRNA content and SREBP1-binding to Slc2a4 promoter. Finally, the small ubiquitin-modifier conjugating enzyme 9 (UBC9), whose low content indicates accelerated GLUT4 degradation was analyzed in soleus.

KEY FINDINGS: Hypercorticosteronemia, hyperinsulinemia and low glucose decay rate in the insulin tolerance test of obese rats were restored by CBX (P < 0.05). Slc2a4/GLUT4 increased in SAT (P < 0.05) and decreased in VAT (P < 0.01) of obese rats. In soleus, obesity increased Slc2a4 but decreased GLUT4 (P < 0.01), possibly by accelerating GLUT4 degradation, as suggested by decreased UBC9 (P < 0.01). CBX restored both UBC9 and GLUT4 contents. SREBP1 did not participate in the Slc2a4 transcriptional regulation.

SIGNIFICANCE: The insulin sensitizer effect of CBX involves the increase of GLUT4 expression in soleus, indicating an increased glucose disposal in skeletal muscle. This observation reinforces the skeletal muscle as the main site of insulin-induced glucose uptake and sheds new light on the metabolic effects of 11βHSD1 inhibitors, since most of the studies so far have focused on its effects on liver and adipose tissues.

PMID:31077719 | DOI:10.1016/j.lfs.2019.05.017