Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Geriatrics, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai, China.
J Cell Mol Med. 2021 Jul;25(14):6855-6863. doi: 10.1111/jcmm.16692. Epub 2021 Jun 4.
BECN1, a protein essential for autophagy, is involved in adipocyte differentiation, lipolysis and insulin resistance. The discovery of new mechanisms for modifying BECN1 in adipocytes may provide novel therapeutic targets for obesity. This study aimed to investigate the impact of mutations at the acetylation sites of BECN1 on adipocyte differentiation and lipolysis. We found that Ace-BECN1 levels were increased in 3T3-L1 adipocyte differentiation and isoproterenol-/TNF-α-stimulated lipolysis and in subcutaneous and visceral adipose tissues of high-fat diet mice. K414 was identified as an acetylation site of BECN1, which affects the stability of the BECN1 protein. Mutation at K414 of BECN1 affected autophagy, differentiation and lipolysis in 3T3-L1 adipocytes. These data indicated the potential of BECN1 K414 as a key molecule and a drug target for regulating autophagy and lipid metabolism in adipocytes.
BECN1 是自噬所必需的一种蛋白，它参与脂肪细胞分化、脂解和胰岛素抵抗。发现能够修饰脂肪细胞中 BECN1 的新机制，可能为肥胖症提供新的治疗靶点。本研究旨在探讨 BECN1 乙酰化位点突变对脂肪细胞分化和脂解的影响。我们发现，3T3-L1 脂肪细胞分化过程中、异丙肾上腺素/TNF-α 刺激的脂解过程中以及高脂肪饮食诱导的小鼠皮下和内脏脂肪组织中 Ace-BECN1 水平升高。鉴定出 BECN1 的 K414 为乙酰化位点，该位点影响 BECN1 蛋白的稳定性。BECN1 的 K414 突变影响 3T3-L1 脂肪细胞中的自噬、分化和脂解。这些数据表明，BECN1 的 K414 作为一个关键分子和药物靶点，具有调节脂肪细胞自噬和脂质代谢的潜力。
