611-P: Berberine Prevented High-Fat Diet-Induced Metabolic Disorders via Inhibition of Whole Lipid Metabolism

Berberine, an alkaloid extracted from coptis and phellodendron, is known to alleviate lipid metabolism disorders, but the precise molecular mechanism remains unknown. This study aimed to investigate whether berberine regulated lipid metabolism by mitochondrial complex I suppression. In this study, the mitochondrial complex I inhibitor rotenone was used parallel to explore whether the lipid-lowering action of BBR was related to complex I. B6 mice were fed with high-fat diet (HFD) with or without berberine or rotenone for 20 weeks. Obesity, hepatic steatosis and insulin resistance were induced by HFD and reversed by berberine. Additionally, berberine reduced HFD induced complex I-dependent oxidative phosphorylation of gut and liver, citrate synthase activity, mtDNA copy number and ATP synthesis in liver. It also inhibited lipid synthesis, fatty acid uptake and oxidation. Furthermore, berberine increased the length and decreased the density of mitochondria to facilitate mitochondrial fusion. Berberine promoted the intestinal lipid excretion as well as reduced the abundance and diversity of gut microbiota remarkably. Nevertheless, no changes in metabolism and mitochondrial function of the recipient mice were observed after transplantation of fecal microbiota from the berberine treated mice. In vitro, berberine normalized oleic acid induced lipid deposition of mouse primary hepatocytes significantly. Oleic acid decreased AMPK activity, which was activated by berberine. The lipid-lowering effects of berberine were unaffected in the presence of compound C, an AMPK inhibitor. In all experiments, rotenone showed similar effects as berberine except for the little alteration of gut bacteria. In conclusion, these results suggested that mitochondrial complex I of gut and liver is the target of berberine. Berberine and rotenone alleviates obesity and hepatic steatosis independently of gut microbiota and AMPK activity. Disclosure M. Yu: None. M. Alimujiang: None. J. Yin: None. Funding National Natural Science Foundation of China (81670790)