Aberrant elevation of FTO levels promotes liver steatosis by decreasing the m6A methylation and increasing the stability of SREBF1 and ChREBP mRNAs.

ABSTRACT: Previous studies have indicated an association of fat mass and obesity-associated (FTO) with nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide. This study aimed to decipher the complex role of FTO in hepatic lipid metabolism. We found that a decrease in N6-methyladenosine (m6A) RNA methylation in the liver of mice fed with a high-fat diet (HFD) was accompanied by an increase in FTO expression. Overexpression of FTO in the liver promoted triglyceride accumulation by upregulating the expression of lipogenic genes. Mechanistical studies revealed that FTO could stabilize the mRNAs of sterol regulatory element binding transcription factor 1 (SREBF1) and carbohydrate responsive element binding protein (ChREBP), two master lipogenic transcription factors, b

SUBMITTER: Tang Z 

PROVIDER: S-EPMC9951264 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature