Stimulator of Interferon Genes (STING) Triggers Adipocyte Autophagy
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 adi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/19/2345 |
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| author | Kornél Z. Varga Katalin Gyurina Ádám Radványi Tibor Pál László Sasi-Szabó Haidong Yu Enikő Felszeghy Tamás Szabó Tamás Röszer |
| author_facet | Kornél Z. Varga Katalin Gyurina Ádám Radványi Tibor Pál László Sasi-Szabó Haidong Yu Enikő Felszeghy Tamás Szabó Tamás Röszer |
| author_sort | Kornél Z. Varga |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T21:47:39Z |
| format | Article |
| id | doaj.art-742933cda5f14eefb8ca14b100d35a37 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T21:47:39Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-742933cda5f14eefb8ca14b100d35a372023-11-19T14:12:27ZengMDPI AGCells2073-44092023-09-011219234510.3390/cells12192345Stimulator of Interferon Genes (STING) Triggers Adipocyte AutophagyKornél Z. Varga0Katalin Gyurina1Ádám Radványi2Tibor Pál3László Sasi-Szabó4Haidong Yu5Enikő Felszeghy6Tamás Szabó7Tamás Röszer8Pediatric Obesity Research Division, Institute of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryPediatric Obesity Research Division, Institute of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryPediatric Obesity Research Division, Institute of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryPediatric Obesity Research Division, Institute of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryPediatric Obesity Research Division, Institute of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryInstitute of Neurobiology, Ulm University, 89081 Ulm, GermanyPediatric Obesity Research Division, Institute of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryPediatric Obesity Research Division, Institute of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryPediatric Obesity Research Division, Institute of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryInnate 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.https://www.mdpi.com/2073-4409/12/19/2345adipocyteinflammationimmunitySTINGinterferonsmitochondria |
| spellingShingle | Kornél Z. Varga Katalin Gyurina Ádám Radványi Tibor Pál László Sasi-Szabó Haidong Yu Enikő Felszeghy Tamás Szabó Tamás Röszer Stimulator of Interferon Genes (STING) Triggers Adipocyte Autophagy Cells adipocyte inflammation immunity STING interferons mitochondria |
| title | Stimulator of Interferon Genes (STING) Triggers Adipocyte Autophagy |
| title_full | Stimulator of Interferon Genes (STING) Triggers Adipocyte Autophagy |
| title_fullStr | Stimulator of Interferon Genes (STING) Triggers Adipocyte Autophagy |
| title_full_unstemmed | Stimulator of Interferon Genes (STING) Triggers Adipocyte Autophagy |
| title_short | Stimulator of Interferon Genes (STING) Triggers Adipocyte Autophagy |
| title_sort | stimulator of interferon genes sting triggers adipocyte autophagy |
| topic | adipocyte inflammation immunity STING interferons mitochondria |
| url | https://www.mdpi.com/2073-4409/12/19/2345 |
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