kukoamine-a and Non-alcoholic-Fatty-Liver-Disease

Nonalcoholic fatty liver disease (NAFLD) refers to a pathological condition of hepatic steatosis. Insulin resistance is believed to be the key mechanism mediating initial accumulation of fat in the liver, resulting in hepatic steatosis. Kukoamine A (KuA), a spermine alkaloid, is a major bioactive component extracted from the root barks of Lycium chinense (L. chinense) Miller. In the current study, we aimed to explore the possible effect of KuA on insulin resistance and fatty liver. We showed that KuA significantly inhibited the increase of fasting blood glucose level and insulin level, and the glucose levels in response to glucose and insulin load in HFD-fed mice, which was in a dose-dependent manner. KuA dose-dependently decreased the histological injury of liver, levels of hepatic triglyceride (TG), and serum AST and ALT activities in HFD-fed mice. The increase of serum levels of TNFɑ, IL-1β, IL-6 and C reactive protein in HFD-fed mice was inhibited by KuA. HFD feeding-induced increase of hepatic expression of Srebp-1c and its target genes, including fatty acid synthase (FAS) and acetyl CoA carboxylase 1 (ACC1), was significantly inhibited by KuA. Moreover, upregulation of Srebp-1c notably inhibited KuA-induced improvement of insulin-stimulated glucose uptake, decrease of lipid accumulation and H

Topics: Animals; Dietary Fats; Dose-Response Relationship, Drug; Gene Expression Regulation; Insulin Resistance; Mice; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Random Allocation; Spermine; Sterol Regulatory Element Binding Protein 1