Kosacka J, Kern M, Klöting N, Paeschke S, Rudich A, Haim Y, Gericke M, Serke H, Stumvoll M, Bechmann I, Nowicki M, Blüher M
Department of Medicine, University of Leipzig, Liebigstraße 21, D-04103 Leipzig, Germany.
Department of Medicine, University of Leipzig, Liebigstraße 21, D-04103 Leipzig, Germany.
Mol Cell Endocrinol. 2015 Jul 5;409:21-32. doi: 10.1016/j.mce.2015.03.015. Epub 2015 Mar 26.
Pathophysiology of obesity is closely associated with enhanced autophagy in adipose tissue (AT). Autophagic process can promote survival or activate cell death. Therefore, we examine the occurrence of autophagy in AT of type 2 diabetes (T2D) patients in comparison to obese and lean individuals without diabetes.
METHODOLOGY/PRINCIPAL FINDINGS: Numerous autophagosomes accumulated within adipocytes were visualized by electron transmission microscopy and by immunofluorescence staining for autophagy marker LC3 in obese and T2D patients. Increased autophagy was demonstrated by higher LC3-II/LC3-I ratio, up-regulated expression of LC3 and Atg5 mRNA, along with decreased p62 and mTOR protein levels. Increased autophagy occurred together with AT inflammation.
Our data suggest fat depot-related differences in autophagy regulation. In subcutaneous AT, increased autophagy is accompanied by increased markers of apoptosis in patients with obesity independently of T2D. In contrast, in visceral AT only in T2D patients increased autophagy was related to higher markers of apoptosis.
肥胖的病理生理学与脂肪组织（AT）中自噬增强密切相关。自噬过程可促进存活或激活细胞死亡。因此，我们比较了2型糖尿病（T2D）患者与无糖尿病的肥胖和瘦个体脂肪组织中自噬的发生情况。
方法/主要发现：通过电子透射显微镜和自噬标记物LC3的免疫荧光染色观察到肥胖和T2D患者脂肪细胞内积累了大量自噬体。较高的LC3-II/LC3-I比值、LC3和Atg5 mRNA表达上调以及p62和mTOR蛋白水平降低表明自噬增加。自噬增加与脂肪组织炎症同时发生。
我们的数据表明自噬调节存在脂肪储存部位相关差异。在皮下脂肪组织中，肥胖患者（无论是否患有T2D）自噬增加的同时凋亡标志物也增加。相反，在内脏脂肪组织中，仅T2D患者自噬增加与较高的凋亡标志物相关。
