Beneficial Effects of Berberine on Nonalcoholic Fatty Liver Disease (NAFLD)

Nonalcoholic fatty liver disease (NAFLD) is currently a worldwide problem associated with diabetes, obesity, heart diseases, and insulin resistance. The pathogenesis of NAFLD is divided into simple steatosis, through nonalcoholic steatohepatitis (NASH) to fibrosis and cirrhosis finally, lipid deposition and chronic inflammation are the main markers. There is still no effective medicine for the therapy of NAFLD, specifically in the NASH stage. Berberine (BBR) is a natural product isolated from plants such as Coptis chinensis Franch, and it has been reported it had beneficial pharmacological activities in a series of metabolic diseases, focusing on adenosine monophosphate-activated protein kinase (AMPK) pathway. BBR showed anti-hyperglycemic and anti-hyperlipidemic effects in diabetes and obesity patients and animal models. It improved insulin sensitivity in these reports and our experiment. We found BBR improved insulin resistance and glucose intolerance in HFD mice, without body weight or food intake difference. BBR ameliorates fat deposition in liver, through reducing lipogenesis related genes expression. Meanwhile, BBR decreased inflammation in liver and adipose tissue. BBR inhibited JNK pathway and activated AMPK phosphorylation in hepatocytes, but not in the macrophages. Thus, the function cells may be the main cell type that responds to BBR in liver, and maybe BBR down-regulates lipogenesis through inhibiting Akt