ArticleThe Journal of clinical investigation2022
Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 54 citations in OpenAlex.
- Advanced nanoformulations of NUAK1 regulate NLRP3 inflammasome for preeclampsia management in mice.Nature communications · 2026Article
- Innate immune signalling in the adipocyte.Journal of biochemistry · 2026Review
- Caspase-1/11 deficiency and cold exposure enhance the anti-tumor activity of brown adipose tissue secretome against breast cancer cells.Cancer & metabolism · 2026Article
- Mitochondrial DNA efflux as a potential amplifier of systemic inflammatory network rewiring in heart failure with preserved ejection fraction.Frontiers in immunology · 2026Review
- Sodium selenite attenuates sepsis-induced cardiac inflammation and oxidative injury by regulating TXN2/TXNIP/NLRP3 signaling and ferroptosis.Frontiers in pharmacology · 2026Article
- Molecular Mechanisms of cGAS-STING Axis and Mitochondrial Dysfunction-Related Diseases in Humans: A Comprehensive Review.Current neuropharmacology · 2026Review
- H3K18 lactylation-mediated SPHK1-SIRT1 feedback loop accelerates pyroptosis of tubular epithelial cells in sepsis-associated acute kidney injury.Theranostics · 2026Article
- ACLY Safeguards Copper Homeostasis to Sustain Brown Adipose Tissue Thermogenesis and Restrain Diet-Induced Obesity.Research (Washington, D.C.) · 2026Article
- Obesity and Exercise: New Insights and Perspectives.Endocrine reviews · 2025Review
- Bidirectional Relationship Between Anaesthetic Drugs and Metabolic Syndrome: Clinical Effects and Mechanisms.Journal of cellular and molecular medicine · 2025Review
- Elevation of ISG15 promotes diabetic kidney disease by modulating renal tubular epithelial cell pyroptosis.Clinical and translational medicine · 2025Article
- Role of MS4A7 in Regulating Microglial Polarization and Neuroinflammation in Spinal Cord Injury via the cGAS-STING-NLRP3 Axis.CNS neuroscience & therapeutics · 2025Article
- NLRP3 inflammasome-mediated disruption of mitochondrial homeostasis in alveolar macrophages contributes to ozone-induced acute lung inflammatory injury.Acta biochimica et biophysica Sinica · 2025Article
- Mitochondrial DNA in atherosclerosis research progress: a mini review.Frontiers in immunology · 2025Review
- Resveratrol improved mitochondrial biogenesis by activating SIRT1/PGC-1α signal pathway in SAP.Scientific reports · 2024Article
- Review
- cGAS-STING, inflammasomes and pyroptosis: an overview of crosstalk mechanism of activation and regulation.Cell communication and signaling : CCS · 2024Review
- Mitochondrial quality control: a pathophysiological mechanism and potential therapeutic target for chronic obstructive pulmonary disease.Frontiers in pharmacology · 2024Review
- The Role of Histone Deacetylases in NLRP3 Inflammasomesmediated Epilepsy.Current molecular medicine · 2024Review
- Altered accumulation of hepatic mitochondrial antioxidant proteins with age and environmental heat stress.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
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9 authors at 3 institutions in 1 country.
Funding
Abstract
Brown adipose tissue (BAT), a crucial heat-generating organ, regulates whole-body energy metabolism by mediating thermogenesis. BAT inflammation is implicated in the pathogenesis of mitochondrial dysfunction and impaired thermogenesis. However, the link between BAT inflammation and systematic metabolism remains unclear. Herein, we use mice with BAT deficiency of thioredoxin-2 (TRX2), a protein that scavenges mitochondrial reactive oxygen species (ROS), to evaluate the impact of BAT inflammation on metabolism and thermogenesis and its underlying mechanism. Our results show that BAT-specific TRX2 ablation improves systematic metabolic performance via enhancing lipid uptake, which protects mice from diet-induced obesity, hypertriglyceridemia, and insulin resistance. TRX2 deficiency impairs adaptive thermogenesis by suppressing fatty acid oxidation. Mechanistically, loss of TRX2 induces excessive mitochondrial ROS, mitochondrial integrity disruption, and cytosolic release of mitochondrial DNA, which in turn activate aberrant innate immune responses in BAT, including the cGAS/STING and the NLRP3 inflammasome pathways. We identify NLRP3 as a key converging point, as its inhibition reverses both the thermogenesis defect and the metabolic benefits seen under nutrient overload in BAT-specific Trx2-deficient mice. In conclusion, we identify TRX2 as a critical hub integrating oxidative stress, inflammation, and lipid metabolism in BAT, uncovering an adaptive mechanism underlying the link between BAT inflammation and systematic metabolism.
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