Division of Endocrinology Diabetes and Metabolism, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Department of Nutrition and Integrative Physiology, University of Utah College of Health and Program in Molecular Medicine, Salt Lake City, UT 84112, USA.
Cell Rep. 2018 Nov 13;25(7):1708-1717.e5. doi: 10.1016/j.celrep.2018.10.040.
Autophagy is a homeostatic cellular process involved in the degradation of long-lived or damaged cellular components. The role of autophagy in adipogenesis is well recognized, but its role in mature adipocyte function is largely unknown. We show that the autophagy proteins Atg3 and Atg16L1 are required for proper mitochondrial function in mature adipocytes. In contrast to previous studies, we found that post-developmental ablation of autophagy causes peripheral insulin resistance independently of diet or adiposity. Finally, lack of adipocyte autophagy reveals cross talk between fat and liver, mediated by lipid peroxide-induced Nrf2 signaling. Our data reveal a role for autophagy in preventing lipid peroxide formation and its transfer in insulin-sensitive peripheral tissues.
自噬是一种参与降解寿命长或受损细胞成分的细胞内稳态过程。自噬在脂肪生成中的作用已得到广泛认可，但在成熟脂肪细胞功能中的作用在很大程度上仍是未知的。我们表明，自噬蛋白 Atg3 和 Atg16L1 是成熟脂肪细胞中线粒体功能所必需的。与先前的研究不同，我们发现，自噬在发育后被剔除会导致外周胰岛素抵抗，而与饮食或肥胖无关。最后，脂肪细胞自噬的缺乏揭示了脂肪和肝脏之间的串扰，由脂质过氧化物诱导的 Nrf2 信号介导。我们的数据揭示了自噬在防止脂质过氧化物形成及其在胰岛素敏感的外周组织中的转移中的作用。
