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Br J Pharmacol. 2018 Jan;175(2):374-387. doi: 10.1111/bph.14079. Epub 2017 Dec 15.

Berberine attenuates hepatic steatosis and enhances energy expenditure in mice by inducing autophagy and fibroblast growth factor 21.

Sun Y1,2, Xia M1,2, Yan H1,2, Han Y3, Zhang F3, Hu Z3, Cui A3, Ma F3, Liu Z3, Gong Q3, Chen X3, Gao J3, Bian H1,2, Tan Y4,5, Li Y3, Gao X1,2.

Author information

1
Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
2
Fudan Institute for Metabolic Diseases, Shanghai, China.
3
CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
4
Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
5
Pediatric Research Institute at the Department of Pediatrics, Wendy L. Novak Diabetes Care Center, University of Louisville, Louisville, KY, USA.

Abstract

BACKGROUND AND PURPOSE:

Berberine, a compound from rhizome coptidis, is traditionally used to treat gastrointestinal infections, such as bacterial diarrhoea. Recently, berberine was shown to have hypoglycaemic and hypolipidaemic effects. We investigated the mechanisms by which berberine regulates hepatic lipid metabolism and energy expenditure in mice.

EXPERIMENTAL APPROACH:

Liver-specific SIRT1 knockout mice and their wild-type littermates were fed a high-fat, high-sucrose (HFHS) diet and treated with berberine by i.p. injection for five weeks. Mouse primary hepatocytes and human HepG2 cells were treated with berberine and then subjected to immunoblotting analysis and Oil Red O staining.

KEY RESULTS:

Berberine attenuated hepatic steatosis and controlled energy balance in mice by inducing autophagy and FGF21. These beneficial effects of berberine on autophagy and hepatic steatosis were abolished by a deficiency of the nutrient sensor SIRT1 in the liver of 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. Mechanistically, the berberine stimulates SIRT1 deacetylation activity and induces autophagy in an autophagy protein 5-dependent manner. Moreover, the administration of berberine was shown to promote hepatic gene expression and circulating levels of FGF21 and ketone bodies in mice in a SIRT1-dependent manner.

CONCLUSIONS AND IMPLICATIONS:

Berberine acts in the liver to regulate lipid utilization and maintain whole-body energy metabolism by mediating autophagy and FGF21 activation. Hence, it has therapeutic potential for treating metabolic defects under nutritional overload, such as fatty liver diseases, type 2 diabetes and obesity.

PMID:
29065221
PMCID:
PMC5758394
DOI:
10.1111/bph.14079
[Indexed for MEDLINE]
Free PMC Article

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