BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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.