Herbacetin, a flaxseed flavonoid, ameliorates high percent dietary fat induced insulin resistance and lipid accumulation through the regulation of hepatic lipid metabolizing and lipid-regulating enzymes

Abstract

Healthy plants and their constituents have been considered as a safe remedy for the treatment of obesity and obesity associated diseases. Herbacetin is a dietary flavonoid that has been explored for many pharmacological activities; but, the anti-hyperglycaemic and anti-hyperlipidemic properties of herbacetin have not yet been explored. The present study was performed to evaluate the ameliorative effect of herbacetin on high-fat diet-induced hyperglycaemia and hyperlipidemia in 57BL/6 J mice. Obesity associated insulin resistance was induced by continuously feeding the mice with high-fat diet for 10 weeks. Afterwards, mice were subjected to intragastric administration of herbacetin (different doses) daily along with high-fat diet for the next 5 weeks. At the end of 106^th day, changes in body weight, blood glucose, insulin, HOMA-IR, and lipids profiles and lipid-regulating enzymes were evaluated. Herbacetin significantly reduced the body weight, plasma glucose, plasma insulin, and HOMA-IR activity in obesity associated insulin resistant mice (OIR). In addition, herbacetin administration significantly reduced the plasma and hepatic total cholesterol, triglycerides, and free fatty acids in OIR mice. Moreover, herbacetin significantly improved the altered hepatic lipid metabolizing and lipid-regulating enzymes such as SREBP-1c, and 2, fatty acid synthase (FAS), fatty acid β-oxidation (β-oxidation), malic enzyme, glucose 6-phosphate dehydrogenase (G6PD), and carnitine palmitoyltransferase (CPT) when compared to OIR control mice. Histopathological examination clearly showed that herbacetin decreases lipid droplets in the liver tissue. Thus, observed results strongly indicate that herbacetin provides remarkable protection against the harmful effects of chronic high-fat diet consumption because of its anti-hyperglycaemic and anti-hyperlipidemic properties through the regulation of hepatic lipid metabolizing and lipid-regulating enzymes.

Keywords: 57BL/6J mice; Anti-hyperglycaemia; Anti-hyperlipidemia; Herbacetin; Insulin resistance; Obesity.