Berberine attenuates hepatic steatosis and enhances energy expenditure. - GreenMedInfo Summary
Berberine Attenuates Hepatic Steatosis and Enhances Energy Expenditure in Mice by Inducing Autophagy and Fibroblast Growth Factor 21.
Br J Pharmacol. 2017 Oct 24. Epub 2017 Oct 24. PMID: 29065221
BACKGROUND AND PURPOSE: Berberine, a compound from rhizome coptidis, is traditionally used to treat gastrointestinal infections, such as bacteria diarrhea. Recently, hypoglycemic and hypolipidemic efficacies of berberine were identified. We investigate mechanisms by which berberine regulates hepatic lipid metabolism and energy expenditure in mice.
EXPERIMENTAL APPROACH: Liver-specific SIRT1 knockout (SIRT1 LKO) mice and their wild-type littermates were fed on a HFHS diet, and then treated with berberine by intraperitoneal injection for five weeks. Mouse primary hepatocytes and human HepG2 cells were treated with berberine, and then subject to immunoblotting analysis and Oil Red O staining.
KEY RESULTS: Berberine attenuates hepatic steatosis and controls energy balance in mice by inducing autophagy and fibroblast growth factor 21. The beneficial effects of berberine to induce autophagy and ameliorate hepatic steatosis are abrogated by the nutrient sensor SIRT1 deficiency in the liver of high-fat, high-sucrose (HFHS) diet-fed obese mice and in mouse primary hepatocytes. SIRT1 is essential for berberine to potentiate autophagy and inhibit lipid storage in mouse livers in response to fasting. Mechanically, berberine stimulates SIRT1 deacetylation activity and induces autophagy in an Atg5-dependent manner. Moreover, administration of berberine is sufficient to promote hepatic gene expression and circulating levels of FGF21 and ketone bodies in mice in a SIRT1 dependent manner.
CONCLUSIONS & IMPLICATIONS: Berberine acts in the liver to regulate lipid utilization and maintain whole-body energy metabolism, and berberine-mediated autophagy and FGF21 activation have the therapeutic potential for treating metabolic defects under nutrition overload, such as fatty liver diseases, type 2 diabetes and obesity.