Reduced oxidative capacity in macrophages results in systemic insulin resistance

Saet Byel Jung, Min Jeong Choi, Dongryeol Ryu, Hyon Seung Yi, Seong Eun Lee, Joon Young Chang, Hyo Kyun Chung, Yong Kyung Kim, Seul Gi Kang, Ju Hee Lee, Koon Soon Kim, Hyun Jin Kim, Cuk Seong Kim, Chul Ho Lee, Robert Williams, Hail Kim, Heung Kyu Lee, Johan Auwerx, Minho Shong

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Oxidative functions of adipose tissue macrophages control the polarization of M1-like and M2-like phenotypes, but whether reduced macrophage oxidative function causes systemic insulin resistance in vivo is not clear. Here, we show that mice with reduced mitochondrial oxidative phosphorylation (OxPhos) due to myeloid-specific deletion of CR6-interacting factor 1 (Crif1), an essential mitoribosomal factor involved in biogenesis of OxPhos subunits, have M1-like polarization of macrophages and systemic insulin resistance with adipose inflammation. Macrophage GDF15 expression is reduced in mice with impaired oxidative function, but induced upon stimulation with rosiglitazone and IL-4. GDF15 upregulates the oxidative function of macrophages, leading to M2-like polarization, and reverses insulin resistance in ob/ob mice and HFD-fed mice with myeloid-specific deletion of Crif1. Thus, reduced macrophage oxidative function controls systemic insulin resistance and adipose inflammation, which can be reversed with GDF15 and leads to improved oxidative function of macrophages.

Original languageEnglish (US)
Article number1551
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

insulin
macrophages
Macrophages
Insulin Resistance
Insulin
mice
deletion
phosphorylation
rosiglitazone
Oxidative Phosphorylation
Polarization
polarization
adipose tissues
biological evolution
Inflammation
phenotype
stimulation
Interleukin-4
Adipose Tissue
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Jung, S. B., Choi, M. J., Ryu, D., Yi, H. S., Lee, S. E., Chang, J. Y., ... Shong, M. (2018). Reduced oxidative capacity in macrophages results in systemic insulin resistance. Nature Communications, 9(1), [1551]. https://doi.org/10.1038/s41467-018-03998-z

Reduced oxidative capacity in macrophages results in systemic insulin resistance. / Jung, Saet Byel; Choi, Min Jeong; Ryu, Dongryeol; Yi, Hyon Seung; Lee, Seong Eun; Chang, Joon Young; Chung, Hyo Kyun; Kim, Yong Kyung; Kang, Seul Gi; Lee, Ju Hee; Kim, Koon Soon; Kim, Hyun Jin; Kim, Cuk Seong; Lee, Chul Ho; Williams, Robert; Kim, Hail; Lee, Heung Kyu; Auwerx, Johan; Shong, Minho.

In: Nature Communications, Vol. 9, No. 1, 1551, 01.12.2018.

Research output: Contribution to journalArticle

Jung, SB, Choi, MJ, Ryu, D, Yi, HS, Lee, SE, Chang, JY, Chung, HK, Kim, YK, Kang, SG, Lee, JH, Kim, KS, Kim, HJ, Kim, CS, Lee, CH, Williams, R, Kim, H, Lee, HK, Auwerx, J & Shong, M 2018, 'Reduced oxidative capacity in macrophages results in systemic insulin resistance', Nature Communications, vol. 9, no. 1, 1551. https://doi.org/10.1038/s41467-018-03998-z
Jung, Saet Byel ; Choi, Min Jeong ; Ryu, Dongryeol ; Yi, Hyon Seung ; Lee, Seong Eun ; Chang, Joon Young ; Chung, Hyo Kyun ; Kim, Yong Kyung ; Kang, Seul Gi ; Lee, Ju Hee ; Kim, Koon Soon ; Kim, Hyun Jin ; Kim, Cuk Seong ; Lee, Chul Ho ; Williams, Robert ; Kim, Hail ; Lee, Heung Kyu ; Auwerx, Johan ; Shong, Minho. / Reduced oxidative capacity in macrophages results in systemic insulin resistance. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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