Impaired macrophage autophagy induces systemic insulin resistance in obesity

Kang YH, Cho MH, Kim JY, Kwon MS, Peak JJ, Kang SW, Yoon SY, Song Y. 2016. Oncotarget 7: 35577-35591.

Speaker: Ruei-Yi Chen (陳瑞怡)                          Time:13:00~14:00, March 15, 2017

Commentator: Hung-Tsung Wu (吳泓璁 博士)  Place: Room 601

Abstract:

Obesity-related chronic inflammation is a key factor in the formation of insulin resistance and leads to metabolic diseases including type 2 diabetes mellitus. Obesity induces adipocyte hypertrophy, adipose tissue apoptosis and monocyte differentiation to M1 inflammatory macrophage. Obesity-related insulin resistance induces oxidative stress in the mitochondria (1) and mitochondrial dysfunction causes reactive oxygen species (ROS) accumulation and activates inflammatory reaction. Autophagy plays important roles in inactivation of inflammasome and elimination of damaged organelles including aberrant mitochondria in macrophages. In addition, autophagy regulates metabolic homeostasis in multiple cell types including β-cell, hepatocyte, adipocyte and tissues. (2). This study explores whether macrophage autophagy regulates obesity-related systemic insulin resistance and inflammation. The authors reveal decreased expression of the autophagy marker LC3-II in high fat diet (HFD)-induced obesity mice. In the macrophage-specific Atg7 knockout mice, autophagy is inhibited accompanied with increase of blood glucose, insulin as well as hepatic steatosis development. The proinflammatory markers of M1 macrophage IL1β and TNFα were also induced, which further increased ROS accumulation. In summary, autophagy maintains insulin sensitivity and glucose tolerance by regulating inflammation and ROS generation in macrophage. Obesity or HFD-induced inflammation may impair autophagy and leads to insulin resistance. Thus, autophagy has the potential to be a therapeutic target for inflammatory diseases including diabetes.

References:

1.    McNelis J, Olefsky J. 2014. Macrophages, Immunity, and Metabolic Disease. Immunity 41:36-48.

2.    Saitoh T, Akira S. 2016. Regulation of inflammasomes by autophagy. J Allergy Clin Immunol 138:28-36.