Salidroside-regulated lipid metabolism with down-regulation of miR-370 in type 2 diabetic mice

Abstract

Salidroside is known for its pharmacological properties and in particular its antioxidation effects. In recent years, it has been recognized that salidroside plays an important role in treating diabetes. Accumulated evidence suggests that microRNAs may be involved in diabetic lipid disorders. We investigated how salidroside regulates lipid metabolism through miR-370 in vivo and in vitro. After 4 weeks of a high-fat diet, and intraperitoneal injection of streptozotocin (100mg/kg), type 2 diabetes was induced in male C56BL/6J mice. After 4 weeks, mice with fasting blood glucose levels above 7.8mmol/l were divided into five groups: those with diabetes mellitus, and those treated with 40mg/kg, 80mg/kg, and 160mg/kg salidroside, and metformin (480mg/kg), for a further 4 weeks. The hypoglycemic effects of salidroside were consistently demonstrated when measuring fasting blood glucose levels, observing insulin-sensitizing effects, and testing oral glucose tolerance. In addition to this, the expressions of miR-370, and related lipid protein expression in primary hepatocytes, were examined in primary type 2 diabetic mice. The present study has shown that the expression levels of miR-370, SREBP-1 and FAS-1 were significantly elevated in the liver of type 2 diabetic mice. In contrast, the elevated expression levels were reversed by salidroside. The addition of salidroside attenuated the effect of miR-370, and reduced the expression of these lipid metabolism proteins in primary hepatocytes. These findings demonstrate that salidroside can directly decrease the expression of miR-370 in type 2 diabetic mice, and particularly in primary hepatocytes, affecting lipid metabolism in the liver.