Berberine Ameliorates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats via Activation of SIRT3/AMPK/ACC Pathway

Curr Med Sci. 2019 Feb;39(1):37-43. doi: 10.1007/s11596-019-1997-3. Epub 2019 Mar 13.

Abstract

This study aimed to verify the effects of berberine (BBR) on the fat metabolism proteins involved in the sirtuin 3 (SIRT3)/adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) pathway in the liver tissues of rats with high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD). Forty-eight rats were randomly divided into the normal control (NC) group, HFD group or BBR group, with 16 rats in each group. After 8 and 16 weeks of treatment, serum and liver samples were collected. Subsequently, body parameters, biochemical parameters and liver pathology were examined. The expression levels of proteins involved in the SIRT3/AMPK/ACC pathway in the liver were detected by Western blotting. After 8 and 16 weeks of a HFD, the successful establishment of rat models with different degrees of NAFLD was confirmed by hematoxylin and eosin (H&E) and Oil Red O staining. NAFLD rat models exhibited obesity and hyperlipidemia, and the protein expression levels of SIRT3, p-AMPK, p-ACC, and CPT-1A in the liver were significantly decreased compared to those in the NC group. The concurrent administration of BBR with the HFD effectively improved serum and liver lipid profiles and ameliorated liver injury. Furthermore, the protein expression levels of SIRT3, p-AMPK, p-ACC, and CPT-1A in the liver were significantly increased in the BBR group as compared with those in the HFD group. In conclusion, our data suggest that the mechanism by which BBR ameliorates HFD-induced hepatic steatosis may be related to the activation of the SIRT3/AMPK/ACC pathway in the liver.

Keywords: berberine; lipid metabolism; non-alcoholic fatty liver disease; sirtuin 3.

MeSH terms

  • Acetyl-CoA Carboxylase / metabolism
  • Adenylate Kinase / metabolism
  • Animals
  • Berberine / administration & dosage*
  • Berberine / pharmacology
  • Carnitine O-Palmitoyltransferase / metabolism
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Lipid Metabolism / drug effects
  • Male
  • Non-alcoholic Fatty Liver Disease / chemically induced
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Obesity / chemically induced*
  • Obesity / complications
  • Obesity / metabolism
  • Phosphorylation / drug effects
  • Random Allocation
  • Rats
  • Signal Transduction / drug effects*
  • Sirtuins / metabolism

Substances

  • SIRT3 protein, rat
  • Berberine
  • Carnitine O-Palmitoyltransferase
  • carnitine palmitoyltransferase-1a, rat
  • Adenylate Kinase
  • Sirtuins
  • Acetyl-CoA Carboxylase