ArticleThe Journal of biological chemistry
Inflammation promotes adipocyte lipolysis via IRE1 kinase.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 63 citations in OpenAlex.
- Boiogito Ameliorates Inflammation-Associated Adipocyte Dysfunction and Restores Adipogenesis in Association with Suppression of NF-κB Signaling.Current issues in molecular biology · 2026Article
- Lymphocyte Antigen 6G Mediates Vagotomy-Associated Reduction in Body Weight.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Sarcopenia and sepsis fuel a self-perpetuating cycle of immunometabolism decline.Frontiers in immunology · 2026Review
- Potential mechanisms and effects of AFB1-induced asthma: A comprehensive analysis based on network toxicology and molecular docking.PloS one · 2026Article
- Article
- Temporal Relationship Between Visceral Fat and Inflammation, and Their Joint Effect on Cardiometabolic Diseases: Evidence from the China Health and Retirement Longitudinal Study (CHARLS).Journal of inflammation research · 2025Article
- CRF1 and ACTH inhibitors are a promising approach to treat obesity and leptin and insulin resistance.Frontiers in endocrinology · 2025Review
- The probioticInternational journal of medical sciences · 2025Article
- TLR4 and prostaglandin pathways at the crossroads of endotoxemia-induced lipolysis.Frontiers in immunology · 2025Article
- Berberine Improves Glucose and Lipid Metabolism in Obese Mice Through the Reduction of IRE1/GSK-3β Axis-Mediated Inflammation.Endocrine, metabolic & immune disorders drug targets · 2025Article
- Association of systemic immune-inflammation index with body mass index, waist circumference and prevalence of obesity in US adults.Scientific reports · 2024Article
- Calmodulin Contributes to Lipolysis and Inflammatory Responses in Clinical Ketosis Cows through the TLR4/IKK/NF-κB Pathway.Animals : an open access journal from MDPI · 2024Article
- IRE1α: from the function to the potential therapeutic target in atherosclerosis.Molecular and cellular biochemistry · 2024Review
- Endotoxin-induced alterations of adipose tissue function: a pathway to bovine metabolic stress.Journal of animal science and biotechnology · 2024Review
- Age-associated accumulation of B cells promotes macrophage inflammation and inhibits lipolysis in adipose tissue during sepsis.Cell reports · 2024Article
- Gut microbiota in overweight and obesity: crosstalk with adipose tissue.Nature reviews. Gastroenterology & hepatology · 2024Review
- Excessive or sustained endoplasmic reticulum stress: one of the culprits of adipocyte dysfunction in obesity.Therapeutic advances in endocrinology and metabolism · 2024Review
- Maackiain Mimics Caloric Restriction throughInternational journal of molecular sciences · 2023Article
- Adipose tissue lipid metabolism: lipolysis.Current opinion in genetics & development · 2023Review
- Low-quality protein modulates inflammatory markers and the response to lipopolysaccharide insult: the case of lysine.The British journal of nutrition · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity associates with inflammation, insulin resistance, and higher blood lipids. It is unclear if immune responses facilitate lipid breakdown and release from adipocytes via lipolysis in a separate way from hormones or adrenergic signals. We found that an ancient component of ER stress, inositol-requiring protein 1 (IRE1), discriminates inflammation-induced adipocyte lipolysis versus lipolysis from adrenergic or hormonal stimuli. Our data show that inhibiting IRE1 kinase activity was sufficient to block adipocyte-autonomous lipolysis from multiple inflammatory ligands, including bacterial components, certain cytokines, and thapsigargin-induced ER stress. IRE1-mediated lipolysis was specific for inflammatory triggers since IRE1 kinase activity was dispensable for isoproterenol and cAMP-induced lipolysis in adipocytes and mouse adipose tissue. IRE1 RNase activity was not associated with inflammation-induced adipocyte lipolysis. Inhibiting IRE1 kinase activity blocked NF-κB activation, interleukin-6 secretion, and adipocyte-autonomous lipolysis from inflammatory ligands. Inflammation-induced lipolysis mediated by IRE1 occurred independently from changes in insulin signaling in adipocytes, suggesting that inflammation can promote IRE1-mediated lipolysis independent of adipocyte insulin resistance. We found no role for canonical unfolded protein responses or ABL kinases in linking ER stress to IRE1-mediated lipolysis. Adiponectin-Cre-mediated IRE1 knockout in mice showed that adipocyte IRE1 was required for inflammatory ligand-induced lipolysis in adipose tissue explants and that adipocyte IRE1 was required for approximately half of the increase in blood triglycerides after a bacterial endotoxin-mediated inflammatory stimulus in vivo. Together, our results show that IRE1 propagates an inflammation-specific lipolytic program independent from hormonal or adrenergic regulation. Targeting IRE1 kinase activity may benefit metabolic syndrome and inflammatory lipid disorders.
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Registered trials
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.