Stimulator of Interferon Genes (STING) Triggers Adipocyte Autophagy

Cells. 2023 Sep 24;12(19):2345. doi: 10.3390/cells12192345.

Abstract

Innate immune signaling in adipocytes affects systemic metabolism. Cytosolic nucleic acid sensing has been recently shown to stimulate thermogenic adipocyte differentiation and protect from obesity; however, DNA efflux from adipocyte mitochondria is a potential proinflammatory signal that causes adipose tissue dysfunction and insulin resistance. Cytosolic DNA activates the stimulator of interferon response genes (STING), a key signal transducer which triggers type I interferon (IFN-I) expression; hence, STING activation is expected to induce IFN-I response and adipocyte dysfunction. However, we show herein that mouse adipocytes had a diminished IFN-I response to STING stimulation by 2'3'-cyclic-GMP-AMP (cGAMP). We also show that cGAMP triggered autophagy in murine and human adipocytes. In turn, STING inhibition reduced autophagosome number, compromised the mitochondrial network and caused inflammation and fat accumulation in adipocytes. STING hence stimulates a process that removes damaged mitochondria, thereby protecting adipocytes from an excessive IFN-I response to mitochondrial DNA efflux. In summary, STING appears to limit inflammation in adipocytes by promoting mitophagy under non-obesogenic conditions.

Keywords: STING; adipocyte; immunity; inflammation; interferons; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Animals
  • Autophagy*
  • DNA, Mitochondrial / metabolism
  • Humans
  • Inflammation
  • Interferon Type I* / metabolism
  • Membrane Proteins* / metabolism
  • Mice

Substances

  • DNA, Mitochondrial
  • Interferon Type I
  • Membrane Proteins
  • STING1 protein, human
  • Sting1 protein, mouse

Grants and funding

This study was supported by a German Research Fund (DFG, RO 4856-1/3 to T.R.), a Hungarian Research Fund (OTKA-NKFI 142939, to T.R.), Bolyai Research Scholarship of the Hungarian Academy of Sciences. (to T.R.), intramural funding from the Foundation of the Institute of Pediatrics, University of Debrecen, Hungary. APC was supported by the University of Debrecen, Hungary.