Reduced oxidative capacity in macrophages results in systemic insulin resistance and its reversal with GDF15 treatment

Identification: Jung, Saet Byel


Description

Reduced oxidative capacity in macrophages results in systemic insulin resistance and its reversal with GDF15 treatment.
  1. Saet-Byel Jung1, Min Jeong Choi1, Dongryeol Ryu2, Hyon-Seung Yi1, Seong Eun Lee1, Joon Young Chang1, Hyo Kyun Chung1, Seul Gi Kang1, Ju Hee Lee1, Cuk-Seong Kim3, Johan Auwerx2, and Minho Shong1
  2. 1Research Center for Endocrine and Metabolic Diseases, Department of Medical Science, School of Medicine, Chungnam National University, Daejeon 35015, Korea
  3. 2Laboratory for Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
  4. 3Department of Physiology, Department of Medical Science, School of Medicine, Chungnam National University, Daejeon 35015, Korea

 
Abstract
 Oxidative functions of adipose tissue macrophages determine the polarized phenotypes M1-like and M2-like activation state, but it remains unclear whether reduced macrophage oxidative function causes systemic insulin resistance in vivo. In this study, we found that mice with reduced mitochondrial OxPhos function due to myeloid cell-specific deletion of CR6-interacting factor 1 (Crif1), an essential mitoribosomal factor involved in biogenesis of OxPhos subunits, exhibited M1-like polarization of macrophages and systemic insulin resistance with adipose inflammation. Macrophage GDF15 expression was reduced in mice with impaired oxidative function, but induced upon stimulation with rosiglitazone and interleukin (IL)-4. GDF15 upregulated the oxidative function of macrophages, leading to M2-like polarization, and reversed insulin resistance in ob/ob mice and HFD-fed mice harboring myeloid cell-specific deletion of Crif1. Thus, reduced macrophage oxidative function determines systemic insulin resistance and adipose inflammation which can be reversed with GDF15 which may improves oxidative function of macrophages.
 
 
 

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