Berberine Alleviates Non-alcoholic Hepatic Steatosis Partially by Promoting SIRT1 Deacetylation of CPT1A in Mice

Overview

Journal Gastroenterol Rep (Oxf)

Specialty Gastroenterology

Date 2023 Jun 9

PMID 37293270

Authors

Peng Wang

Ruikai Li

Yuqi Li

Siwei Tan

Jie Jiang

Huiling Liu

Xiuqing Wei

Affiliations

Soon will be listed here.

Abstract

Background: Berberine effectively alleviates non-alcoholic fatty liver disease (NAFLD). Nevertheless, the mechanism is incompletely comprehended. It has been reported that SIRT1 mediates lipid metabolism in liver and berberine promotes the expression of in hepatocytes. We hypothesized that SIRT1 mediated the effect of berberine on NAFLD.

Methods: The effects of berberine on NAFLD were evaluated in C57BL/6J mice fed a high-fat diet (HFD) and in mouse primary hepatocytes and cell lines exposed to palmitate. The change of fatty acid oxidation (FAO) and the activity of CPT1A were observed in HepG2 cells. Quantitative real-time polymerase chain reaction and Western blot were employed to observe the expression of and lipid metabolism-related molecules. The interaction between SIRT1 and CPT1A was investigated by using co-immunoprecipitation assay in HEK293T cells.

Results: Berberine treatment attenuated hepatic steatosis, reduced triglyceride (190.1 ± 11.2 μmol/g liver vs 113.6 ± 7.6 μmol/g liver, 0.001) and cholesterol (11.3 ± 2.5 μmol/g liver vs 6.3 ± 0.4 μmol/g liver, 0.001) concentration in the liver, and improved lipid and glucose metabolism disorders compared with the HFD group. The expression of was reduced in the liver of NAFLD patients and mouse models. Berberine increased the expression of and promoted the protein level of and its activity in HepG2 cells. overexpression mimicked the effect of berberine on reducing triglyceride levels in HepG2 cells, whereas knock-down attenuated the effect of berberine. Mechanistically, berberine increased the expression of . SIRT1 deacetylated CPT1A at the Lys675 site, which suppressed its ubiquitin-dependent degradation, thereby promoting FAO and alleviating non-alcoholic liver steatosis.

Conclusions: Berberine promoted SIRT1 deacetylation of CPT1A at the Lys675 site, which reduced the ubiquitin-dependent degradation of CPT1A and ameliorated non-alcoholic liver steatosis.

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