title: Berberine reverses abnormal expression of L-type pyruvate kinase by DNA demethylation and histone acetylation in the livers of the non-alcoholic fatty disease rat.
abstract: Berberine (BBR) can potentially be used as a drug against non-alcoholic fatty liver disease (NAFLD) and diabetes. Our previous study found that BBR could change the pattern of DNA methylation. But the mechanisms underlying berberine are still far from completely understood. In this study, the function of L-PK in cell metabolism was explored, and high-fat-diet induced SD rats NAFLD models were created. The NAFLD rats were randomly grouped to be oral administration with BBR at a dosage of 200 mg/kg daily. Then DNA methylation and histone acetylation around the L-type Pyruvate Kinase (L-PK) gene were examined. In the results, we found that L-PK had a positive effect on cell proliferation, glucose utilization and triglyceride metabolism. However, the expression of L-PK was reduced in the livers of NAFLD rats, in accord with the decrease of DNA hypermethylation and histone deacetylation in the regulatory regions of L-PK. Notably, BBR treatment can restore the expression of L-PK by the demethylation of L-PK promoter and the increase in acetylation levels of histone H3 and H4 around L-PK, which indicated that BBR may be a potential drug for epigenetic-included diseases.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics and Ministry of Education, Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University Shanghai, China.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Xinxia
authors.initials: X
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics and Ministry of Education, Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University Shanghai, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Song
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics and Ministry of Education, Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics and Ministry of Education, Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University Shanghai, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics and Ministry of Education, Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University Shanghai, China.
authors.forename: Daru
authors.initials: D
authors.lastname: Lu
keywords: Berberine; DNA methylation; L-type pyruvate kinase; histone acetylation; non-alcoholic fatty liver disease