Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
Department of Biological Sciences, Center for Adipocyte Structure-Function, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Republic of Korea.
Diabetes. 2021 Jan;70(1):182-195. doi: 10.2337/db19-1239. Epub 2020 Oct 12.
/ is a core component of the class III phosphatidylinositol 3-kinase required for autophagosome formation and vesicular trafficking. Although has been implicated in numerous diseases such as cancer, aging, and neurodegenerative disease, the role of in white adipose tissue and related metabolic diseases remains elusive. In this study, we show that adipocyte-specific knockout mice develop severe lipodystrophy, leading to adipose tissue inflammation, hepatic steatosis, and insulin resistance. Ablation of in adipocytes stimulates programmed cell death in a cell-autonomous manner, accompanied by elevated endoplasmic reticulum (ER) stress gene expression. Furthermore, we observed that depletion sensitized mature adipocytes to ER stress, leading to accelerated cell death. Taken together, these data suggest that adipocyte would serve as a crucial player for adipocyte survival and adipose tissue homeostasis.
/ 是 III 类磷脂酰肌醇 3-激酶的核心组成部分，对于自噬体的形成和囊泡运输至关重要。虽然 / 已被牵涉到多种疾病中，如癌症、衰老和神经退行性疾病，但它在白色脂肪组织和相关代谢疾病中的作用仍不清楚。在这项研究中，我们发现脂肪细胞特异性敲除 / 的小鼠会发生严重的脂肪营养不良，导致脂肪组织炎症、肝脂肪变性和胰岛素抵抗。脂肪细胞中 / 的缺失以细胞自主的方式刺激程序性细胞死亡，伴随着内质网（ER）应激基因表达的升高。此外，我们观察到 / 的耗竭使成熟脂肪细胞对 ER 应激敏感，导致细胞死亡加速。总之，这些数据表明，脂肪细胞中的 / 将作为脂肪细胞存活和脂肪组织稳态的关键参与者。
