Effect of silymarin on insulin resistance, GLP-1 and Sirt1 in high fat diet-induced rat model of metabolic syndrome

• Main Authors: Kai-Jyun Chang, 張凱鈞
• Other Authors: 顏國欽
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/11561995289248959217

碩士 === 國立中興大學 === 食品暨應用生物科技學系所 === 103 === High-calorie and high fat diet has been regarded as the major cause of increased prevalence of the metabolic syndrome. Insulin resistance (IR) is the typical symptom of metabolic syndrome, which may lead to type II diabetes mellitus (T2DM). Under IR condition, decreased protein level of sirtulin 1 (Sirt1) and dysregulation of secretion of the gut hormone glucagon-like peptide-1 (GLP-1) which modulate blood glucose balance are observed, which leading to metabolic imbalance and injury of liver and pancreas, and cause the associated complications. Silymarin (SM), flavonoids of milk thistle (Silybum marianum) seed and fruit extracts, has a variety of biological activity, and the most known is protective effect on liver and pancreas. Therefore, the aim of the study was to investgate the effect of SM on abnormalities of blood biochemistry and IR in response to high-fat diet, as well as modulation of GLP-1 and Sirt1. In this study, SD rats were fed with high-fat diet to induce metabolic syndrome symptoms, and intervention of SM (100/200/400 mg/kg b.w.) from 0 week or 8th week of the time course of the experiment, to assess its effect on prevention and improvement of metabolic injury in rats. Results showed that serum TG, LDL, VLDL and other indicators of metabolic syndrome, as well as insulin secretion significantly increased in high-fat diet-induced rats. Besides, HOMA-IR indicated that long-term high-fat diet lead to IR in rats. Interestingly, SM intervention from 0 week or 8th week of experimental period can significantly improve the IR and metabolic syndrome in rats fed with high-fat diet. We also found that SM can improve the impaired glucose tolerance in these rats. Notably, long-term consumption of high-fat diet rats would lead to reduced GLP-1 secretion in rats, while SM intervention from 0 week or 8th week of experimental period, may recover and further enhance GLP-1 secretion in rats fed with high-fat diet. Histopathological analysis showed that high-fat diet may contribute to hepatic steatosis and pancreas fibrosis in rats, and intervention of SM from 0 week can prevent the liver damage caused by high-fat diet. Western blot indicated that decreased Sirt1 protein levels in pancreas and liver were observed in high-fat diet-induced rats, while SM intervention from 0 week of experimental period can recover high-fat diet-impaired Sirt1 protein expression in liver and pancreas of rats. In conclusion, SM can prevent and ameliorate high-fat diet-induced phenomena of IR and dyslipidemia, and can improve the secretion of GLP-1 in rats. SM can also improve fatty liver caused by high-fat diet and enhance Sirt1 protein expression of liver and pancreas in rats. Taken together, SM can prevent and retard the metabolic injury caused by high-fat diet, suggesting that SM may be a potential food factor to improve symptoms of metabolic syndrome.