Hepatic menin recruits SIRT1 to control liver steatosis through histone deacetylation.
Mots clés
Abstrait
OBJECTIVE
The development and progression of non-alcoholic fatty liver disease are associated with aging, obesity, and type 2 diabetes. Understanding the precise regulatory networks of this process will contribute to novel therapeutic strategies.
METHODS
Hepatocyte-specific Men1 knockout mice were generated using Cre/loxP technology. Lipid and glucose metabolic phenotypes and mechanisms were investigated in aging and high-fat diet fed mice.
RESULTS
The expression of menin, encoded by multiple endocrine neoplasia 1 (Men1) gene, is reduced in the liver of aging mice. Hepatocyte-specific deletion of Men1 induces liver steatosis in aging mice. Menin deficiency promotes high-fat diet-induced liver steatosis in mice. Menin recruits SIRT1 to control hepatic CD36 expression and triglyceride accumulation through histone deacetylation.
CONCLUSIONS
Our work reveals that the adaptor protein menin is critical for the progression of hepatic steatosis during aging and metabolic imbalance.
