The Effect Of Pentylmethylquercetin In Metabolic Syndrome Mice Due To Intervention Of Monosodium Glutamate

Background:The"metabolic syndrome"(MetS) is a clustering of Metabolic diseases that reflect overnutrition, sedentary lifestyles, and heredity. Recently, the study for MetS, especially the mechanism and treatment for obesity, become a hot topic. But, a kind of economic and stable MetS animal model is not easy to establish, which may become a bottleneck for study of MetS. Flavonoids have many biological activities, including weight loss, anti-inflammatory, hypoglycemic, improvement of dyslipidemia and insulin resistance and so on which covering almost all aspects of the metabolic syndrome, most likely play an important role in prevention and treatment of metabolic syndrome. Pentylmethylquercetin is a semi-synthesis flavonoid through methylation of quercetin. It has obvious pharmacokinetic advantages.In this study,①we want to establish a full metabolic syndrome mice model through intervention of monosodium glutamate (newborn). Then, we investigated the changes of some gene associated with metabolism in this model.②The study of anti-metabolic syndrome effect of Pentylmethylquercetin in mice. Methods: At 21 days of age, monosodium glutamate (MSG)-treated or saline (Saline)-treated newborn male and female mice were randomly divided into 4 different groups(n=18 mice per group):saline-treated + regular diet group (Saline + RD), monosodium glutamate-treated + regular diet group (MSG + RD), saline-treated + high fat diet group (Saline + HFD), monosodium glutamate treated + high fat diet group (MSG + HFD). At 14 weeks of age, oral glucose tolerance test (n = 6) and intraperitoneal insulin tolerance test (n = 6) tests were performed. The remaining mice in each group (n = 6) continue to fed. At 24 weeks of age, all mice ,wihtout anaesthesia, were sacrificed. Serum levels of glucose, triglyceride, total cholesterol, high density lipoprotein, insulin of each group were measured. RT-PCR assays monitored the expression of adipocytokines (Adiponectin, Leptin), PPARs (PPARα, PPARβ/δ, PPARγ) and the inflammatory cytokines( IL-6, TNF-α) mRNA in the gonadal adipose tissue and liver tissue of mice. Meanwhile, The reproductive capacity test of adult mice was performed: Saline-treated or monosodium glutamate-treated male and female mice (20week, n=8) were randomly matched to observe the reproductive capacity.Results:①M onosodium glutamate intervention (newborn) can induce significant obesity in mice. Lee-index showed a significantly increase. Meanwhile, accompanied by growth inhibition, monosodium glutamate-treated mice manifested as dwarfism-like shape, and infertility.②Blood glucose, triglyceride, total cholesterol, insulin of monosodium glutamate-treated mice showed various degrees of increase, insulin resistance and impaired glucose tolerance have emerged. Interestingly, high-density lipoprotein-cholesterol levels also increased.③RT-PCR analysis suggested, in MSG mice liver and gonadal adipose tissue, some metabolism-related gene expression have seen various degrees of change, including up-regulation of PPARγ, IL-6, TNF-α, leptin mRNA expression; down-regulation of adiponectin, PPARα, PPARβ/δmRNA expression.Conclusion: Either regular diet or high fat diet, monosodium glutamate can cause significant obesity in mice, leading to a comprehensive model of metabolic syndrome, including: central obesity, hyperglycaemia, hyperlipidemia, hypercholesterolemia, hyperinsulinemia, insulin resistance, impaired glucose tolerance and decreased insulin sensitivity. Meanwhile, monosodium glutamate can also induce extensive growth inhibition, and it is an ideal mice model for the study of metabolic syndrome and dwarfism. Methods: At 21 days of age, monosodium glutamate-treated or saline-treated newborn male mice were weaned. After adaptive feeding for two weeks, these mice were randomly divided into 4 different groups at 5 weeks o f age:saline-treated+vehicle group (Control, n=10), monosodium glutamate-treated+vehicle group (Vehicel, n=10), monosodium glutamate-treated+rosiglitazone 5mg/kg group (Ros 5, n=10), monosodium glutamate-treated + Pentylmethylquercetin 20mg/kg group (PMQ 20, n=9). Ros 5 group were administered rosiglitazone with at a dose of 5 mg/kg body weight per day. PMQ 20 group were administered rosiglitazone with at a dose of 20 mg/kg body weight per day. Control group and Vehicel group were administered equipotent volume of vehicle. At 18 weeks of age, all mice ,wihtout anaesthesia, were sacrificed. Serum levels of glucose, triglyceride, total cholesterol, insulin of each group were measured. Organs and adipose tissue were weighted, frozen, prepared test.Result:①PMQ 20mg/kg/d has a significant role in weight loss in MetS mice, comparing with the Vehicle group, showed a significant reduction in body weight, subcutaneous fat and visceral fat weight. 5mg/kg/d rosiglitazone showed a slight increase in body weight .②PMQ 20mg/kg/d can improve glucose and lipid metabolism in MetS mice, especially shows a significant hypoglycemic effect. and the effct tensity is comparable to rosiglitazone 5mg/kg/d.③PMQ 20mg/kg/d can significantly improve insulin resistance in MetS mice.Conclusion: Pentylmethylquercetin has a comprehensive role in the anti-metabolic syndrome, as follows: weight loss, improving glucose and lipid metabolism, improving insulin resistance. Therefore, Pentylmethylquercetin is likely to be a useful clinical drug to prevent and treat metabolic syndrome.