Acetyl-CoA metabolism drives epigenome change and contributes to carcinogenesis risk in fatty liver disease.

ABSTRACT:

Background

The incidence of non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is increasing worldwide, but the steps in precancerous hepatocytes which lead to HCC driver mutations are not well understood. Here we provide evidence that metabolically driven histone hyperacetylation in steatotic hepatocytes can increase DNA damage to initiate carcinogenesis.

Methods

Global epigenetic state was assessed in liver samples from high-fat diet or high-fructose diet rodent models, as well as in cultured immortalized human hepatocytes (IHH cells). The mechanisms linking steatosis, histone acetylation and DNA damage were investigated by computational metabolic modelling as well as through manipulation of IHH cells with metabolic and epigenetic inhibitor

SUBMITTER: Assante G 

PROVIDER: S-EPMC9219160 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature