ArticleProceedings of the National Academy of Sciences of the United States of America2017
DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 197 papers.
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197 citing papers in PubMed, 294 citations in OpenAlex.
- The cGAS-STING pathway in inflammaging and neuroinflammation.Science China. Life sciences · 2026Review
- The cGAS-STING signaling axis in Type 2 diabetes-associated cognitive decline: from mitochondrial DNA sensing to neurodegeneration.Acta diabetologica · 2026Review
- Effects of obesity on brain health and cognition.Nature reviews. Neurology · 2026Review
- Review
- Immunometabolism in Obesity-Associated Type 2 Diabetes: Molecular Mechanisms and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- Natural Small Molecules Targeting Mitochondrial Quality Control for the Treatment of Metabolic Diseases: Mechanisms, Novel Formulations, and Translational Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- NRF2 activation attenuates obesity-induced adipose inflammation by suppressing STING signaling, with depot-specific regulation.Journal of translational medicine · 2026Article
- cGAS-STING signaling in aging and age-related diseases: therapeutic promise and precaution.Archives of pharmacal research · 2026Review
- Intestinal cGAS-STING-IFN signalling promotes obesity by downregulating microbiota-derived IAA in male mice.Nature metabolism · 2026Article
- Tetherin enforces an immunometabolic checkpoint that coordinates glycolytic and interferon signaling in adipocytes.bioRxiv : the preprint server for biology · 2026Article
- cGAS: bridging immunity and metabolic regulation.Journal of molecular cell biology · 2026Review
- DsbA-L safeguards T cell mitochondrial redox homeostasis to restrain Th17 differentiation and colitis.Cell death & disease · 2026Article
- [Research progress on the mechanism of mitochondrial dynamics in diabetic foot ulcers and its related intervention strategies].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2026Review
- The SIRT3-DsbA-L-TFAM axis restrains cGAS-driven metabolic dysfunction-associated steatohepatitis in male mice.Nature communications · 2026Article
- Innate immune signalling in the adipocyte.Journal of biochemistry · 2026Review
- The spatiotemporal dynamics of MAMs: mechanisms, pathologies, and therapeutic rewiring.Cellular & molecular biology letters · 2026Review
- Adipocyte-specific NR5A2 deficiency ameliorates diet-induced metabolic syndrome by suppressing adipose tissue inflammation.Scientific reports · 2026Article
- Host mitochondrial DNA in bacterial pathogenesis: Friend, Foe, or Both?Archives of microbiology · 2026Review
- Dietary Protein Restriction Ameliorates Cardiac Inflammaging via AMPK-ULK1-Mediated Mitochondrial Quality Control.Aging cell · 2026Article
- Increased maternal non-esterified fatty acid concentrations during late gestation impair adipose tissue development and metabolic function in Holstein offspring calves.Journal of animal science · 2026Article
137 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the DNA-sensing cGAS-cGAMP-STING pathway. Fat-specific knockout of disulfide-bond A oxidoreductase-like protein (DsbA-L), a chaperone-like protein originally identified in the mitochondrial matrix, impaired mitochondrial function and promoted mtDNA release, leading to activation of the cGAS-cGAMP-STING pathway and inflammatory responses. Conversely, fat-specific overexpression of DsbA-L protected mice against high-fat diet-induced activation of the cGAS-cGAMP-STING pathway and inflammation. Taken together, we identify DsbA-L as a key molecule that maintains mitochondrial integrity. DsbA-L deficiency promotes inflammation and insulin resistance by activating the cGAS-cGAMP-STING pathway. Our study also reveals that, in addition to its well-characterized roles in innate immune surveillance, the cGAS-cGAMP-STING pathway plays an important role in mediating obesity-induced metabolic dysfunction.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.