肝 Menin 通过组蛋白去乙酰化作用招募 SIRT1 以控制肝脂肪变性。
Hepatic menin recruits SIRT1 to control liver steatosis through histone deacetylation.
机构信息
Department of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases and Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
出版信息
J Hepatol. 2013 Dec;59(6):1299-306. doi: 10.1016/j.jhep.2013.07.011. Epub 2013 Jul 16.
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.
背景与目的
非酒精性脂肪性肝病的发生和发展与衰老、肥胖和 2 型糖尿病有关。了解这一过程的确切调控网络将有助于制定新的治疗策略。
方法
利用 Cre/loxP 技术构建了肝细胞特异性 Men1 敲除小鼠。研究了衰老和高脂饮食喂养小鼠的脂质和糖代谢表型及机制。
结果
多发性内分泌肿瘤 1 基因（Men1）编码的 menin 在衰老小鼠肝脏中的表达减少。肝细胞特异性缺失 Men1 可诱导衰老小鼠肝脂肪变性。Menin 缺乏促进高脂饮食诱导的小鼠肝脂肪变性。Menin 通过组蛋白去乙酰化将 SIRT1 募集到控制肝 CD36 表达和甘油三酯积累。
结论
我们的工作表明，接头蛋白 menin 在衰老和代谢失衡期间肝脏脂肪变性的进展中至关重要。
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