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Epigenetic Regulation of Hepatic Lipid Metabolism by DNA Methylation.
Wang, Shirong; Zha, Lin; Cui, Xin; Yeh, Yu-Te; Liu, Ruochuan; Jing, Jia; Shi, Huidong; Chen, Weiping; Hanover, John; Yin, Jun; Yu, Liqing; Xue, Bingzhong; Shi, Hang.
Afiliación
  • Wang S; Department of Biology, Georgia State University, Atlanta, GA, 30303, USA.
  • Zha L; Department of Biology, Georgia State University, Atlanta, GA, 30303, USA.
  • Cui X; The Northern Medical District, Chinese PLA General Hospital, Beijing, 100094, China.
  • Yeh YT; Department of Biology, Georgia State University, Atlanta, GA, 30303, USA.
  • Liu R; Department of Internal Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
  • Jing J; Department of Chemistry and the Center for Diagnosis and Therapeutics, Georgia State University, Atlanta, GA, 30303.
  • Shi H; Department of Biology, Georgia State University, Atlanta, GA, 30303, USA.
  • Chen W; GRU Cancer Center and Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
  • Hanover J; Genomic Core Lab of National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20855, USA.
  • Yin J; Genomic Core Lab of National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20855, USA.
  • Yu L; Department of Chemistry and the Center for Diagnosis and Therapeutics, Georgia State University, Atlanta, GA, 30303.
  • Xue B; Department of Internal Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
  • Shi H; Department of Biology, Georgia State University, Atlanta, GA, 30303, USA.
Adv Sci (Weinh) ; 10(20): e2206068, 2023 07.
Article en En | MEDLINE | ID: mdl-37282749
While extensive investigations have been devoted to the study of genetic pathways related to fatty liver diseases, much less is known about epigenetic mechanisms underlying these disorders. DNA methylation is an epigenetic link between environmental factors (e.g., diets) and complex diseases (e.g., non-alcoholic fatty liver disease). Here, it is aimed to study the role of DNA methylation in the regulation of hepatic lipid metabolism. A dynamic change in the DNA methylome in the liver of high-fat diet (HFD)-fed mice is discovered, including a marked increase in DNA methylation at the promoter of Beta-klotho (Klb), a co-receptor for the biological functions of fibroblast growth factor (FGF)15/19 and FGF21. DNA methyltransferases (DNMT) 1 and 3A mediate HFD-induced methylation at the Klb promoter. Notably, HFD enhances DNMT1 protein stability via a ubiquitination-mediated mechanism. Liver-specific deletion of Dnmt1 or 3a increases Klb expression and ameliorates HFD-induced hepatic steatosis. Single-nucleus RNA sequencing analysis reveals pathways involved in fatty acid oxidation in Dnmt1-deficient hepatocytes. Targeted demethylation at the Klb promoter increases Klb expression and fatty acid oxidation, resulting in decreased hepatic lipid accumulation. Up-regulation of methyltransferases by HFD may induce hypermethylation of the Klb promoter and subsequent down-regulation of Klb expression, resulting in the development of hepatic steatosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metabolismo de los Lípidos / Hígado Graso Límite: Animals Idioma: En Revista: Adv Sci (Weinh) Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metabolismo de los Lípidos / Hígado Graso Límite: Animals Idioma: En Revista: Adv Sci (Weinh) Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
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