0 239

Cited 26 times in

Autophagy deficiency in myeloid cells increases susceptibility to obesity-induced diabetes and experimental colitis

 Hae-Youn Lee  ;  Jinyoung Kim  ;  Wenying Quan  ;  June-Chul Lee  ;  Min-Soo Kim  ;  Seok-Hyung Kim  ;  Jin-Woo Bae  ;  Kyu Yeon Hur  ;  Myung-Shik Lee 
 AUTOPHAGY, Vol.12(8) : 1390-1403, 2016 
Journal Title
Issue Date
Animals ; Autophagy* ; Autophagy-Related Protein 7/metabolism ; Body Weight ; Colitis/metabolism* ; Cytokines/metabolism ; Diabetes Mellitus/etiology ; Diabetes Mellitus/metabolism* ; Diabetes Mellitus, Type 2/metabolism ; Disease Models, Animal ; Disease Progression ; Endoplasmic Reticulum/metabolism ; Female ; Inflammasomes/metabolism ; Inflammation ; Interleukin-1beta/metabolism ; Lipids/chemistry ; Macrophages/metabolism ; Male ; Metabolic Syndrome/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism ; Obesity/complications ; Obesity/metabolism* ; Reactive Oxygen Species/metabolism ; Stromal Cells/metabolism ; T-Lymphocytes, Regulatory/metabolism
autophagy ; colitis ; diabetes ; inflammasome ; macrophages ; obesity
Autophagy, which is critical for the proper turnover of organelles such as endoplasmic reticulum and mitochondria, affects diverse aspects of metabolism, and its dysregulation has been incriminated in various metabolic disorders. However, the role of autophagy of myeloid cells in adipose tissue inflammation and type 2 diabetes has not been addressed. We produced mice with myeloid cell-specific deletion of Atg7 (autophagy-related 7), an essential autophagy gene (Atg7 conditional knockout [cKO] mice). While Atg7 cKO mice were metabolically indistinguishable from control mice, they developed diabetes when bred to ob/w mice (Atg7 cKO-ob/ob mice), accompanied by increases in the crown-like structure, inflammatory cytokine expression and inflammasome activation in adipose tissue. Mφs (macrophages) from Atg7 cKO mice showed significantly higher interleukin 1 β release and inflammasome activation in response to a palmitic acid plus lipopolysaccharide combination. Moreover, a decrease in the NAD(+):NADH ratio and increase in intracellular ROS content after treatment with palmitic acid in combination with lipopolysaccharide were more pronounced in Mφs from Atg7 cKO mice, suggesting that mitochondrial dysfunction in autophagy-deficient Mφs leads to an increase in lipid-induced inflammasome and metabolic deterioration in Atg7 cKO-ob/ob mice. Atg7 cKO mice were more susceptible to experimental colitis, accompanied by increased colonic cytokine expression, T helper 1 skewing and systemic bacterial invasion. These results suggest that autophagy of Mφs is important for the control of inflammasome activation in response to metabolic or extrinsic stress, and autophagy deficiency in Mφs may contribute to the progression of metabolic syndrome associated with lipid injury and colitis.
Full Text
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Lee, Myung Shik(이명식) ORCID logo https://orcid.org/0000-0003-3292-1720
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.