ArticleCell metabolism2019
12-Lipoxygenase Regulates Cold Adaptation and Glucose Metabolism by Producing the Omega-3 Lipid 12-HEPE from Brown Fat.
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Article in Cell metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 123 papers.
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123citing papers in PubMed
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123 citing papers in PubMed, 197 citations in OpenAlex.
- One-Year Effects of High-Intensity Statin on Bioactive Lipids: Findings From the JUPITER Trial.Arteriosclerosis, thrombosis, and vascular biology · 2024Trial
- 6 weeks of fartlek-style endurance training does not alter physiological responses to mild cold exposure but attenuates the cold-induced plasma noradrenaline response: A randomized, matched control trial.Journal of clinical & translational endocrinology · 2026Article
- Adipose tissue as a humoral-neuronal hub in metabolic regulation.Nature reviews. Endocrinology · 2026Review
- Adipocyte Myoglobin Is a Determinant of Energy Expenditure and a Potential Target to Limit Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- EPA-Derived Oxylipin Incorporation into Tissues of High-Fat Diet-Fed Mice and Its Consequences for n-6 PUFA-Derived Oxylipins.The Journal of nutrition · 2026Article
- Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Loss of calcium-dependent phospholipase A2 contributes to multi-omic changes in mouse denervated skeletal muscle.Physiological reports · 2026Article
- Morchella polysaccharide ameliorates myocardial infarction inflammation in mice through increasing gut microbiota-derived 12-HEPE.Acta pharmacologica Sinica · 2026Article
- Emerging complexities of phospholipid metabolism in adipose tissue.Molecules and cells · 2026Review
- Cold exposure and metabolic health: Therapeutic potential for obesity, diabetes, and beyond.Physiological reports · 2026Review
- Comparative proteomic analysis of skin wound healing responses to biomaterial treatments identifies key pathways which govern differential regenerative outcomes.Biomaterials · 2026Article
- Advances in Adipose Tissue Biology.Endocrine reviews · 2026Review
- Review
- Brown adipose tissue and tumor presence: a retrospective association analysis considering the role of body mass index.Lipids in health and disease · 2025Article
- Dietary Full-Fat Rice Bran or Glucose Regulates Bile Acid Circulation, Colonic Microbiota, and Short-Chain Fatty Acids in Pigs During Chronic Cold Stress.Animals : an open access journal from MDPI · 2025Article
- TRPM8-driven thermogenesis by menthol: mechanisms of cold injury prevention.Journal of physiology and biochemistry · 2025Article
- Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025Review
- A two-strata energy flux system driven by a stress hormone prioritizes cardiac energetics.Signal transduction and targeted therapy · 2025Article
- Physiological Conditions, Bioactive Ingredients, and Drugs Stimulating Non-Shivering Thermogenesis as a Promising Treatment Against Diabesity.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Dysregulation of Arachidonic Acid Metabolism Drives Inflammatory Lipid Production in Localized Provoked Vulvodynia.Nutrients · 2025Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
27 authors at 9 institutions in 3 countries.
Luiz Osório LeiriaJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Chih-Hao WangJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Matthew D LynesJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Kunyan YangJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Farnaz ShamsiJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Mari SatoJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Satoru SugimotoJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Emily Y ChenBERG, Framingham, MA, USA.
Valerie BussbergBERG, Framingham, MA, USA.
Niven R NarainBERG, Framingham, MA, USA.
Brian E SansburyCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Justin DarcyJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Tian Lian HuangJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Sean D KodaniJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Masaji SakaguchiJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Andréa L RochaDepartment of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, Brazil.
Tim J SchulzJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA; Department of Adipocyte Development and Nutrition, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
Alexander BarteltDepartment of Genetics and Complex Diseases & Sabri Ülker Center, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University, Munich 80336, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
Gökhan S HotamisligilDepartment of Genetics and Complex Diseases & Sabri Ülker Center, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Michael F HirshmanJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Klaus van LeyenMassachusetts General Hospital, Harvard Medical School, Neuroprotection Research Laboratory, Department of Radiology, Charlestown, MA, USA.
Laurie J GoodyearJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Matthias BlüherDepartment of Medicine, University of Leipzig, Leipzig, Germany.
Aaron M CypessNational Institutes of Health, Bethesda, MD, USA.
Michael A KiebishBERG, Framingham, MA, USA.
Matthew SpiteCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Yu-Hua TsengJoslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA. Electronic address: yu-hua.tseng@joslin.harvard.edu.
Harvard University · USJoslin Diabetes Center · USFramingham State University · USBrigham and Women's Hospital · USGerman Centre for Cardiovascular Research · DEGerman Institute of Human Nutrition · DELeipzig University · DENational Institutes of Health · USUniversidade Estadual de Campinas (UNICAMP) · BR
Funding
SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI JEAN E. SCHAFFER · 1986 to 2026
$50.5MResolution Mechanisms in Acute Inflammation: Resolution PharmacologyP01GM095467 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI SERHAN, CHARLES NICHOLAS · 2011 to 2020
$14.8MTRAINING IN DIABETES AND METABOLISMT32DK007260 · NIDDK · JOSLIN DIABETES CENTER · PI LAURIE J GOODYEAR · 1986 to 2026
$13.6MDevelopmental genes, miRNAs and adipose tissueR01DK082659 · NIDDK · JOSLIN DIABETES CENTER · PI C RONALD KAHN · 2009 to 2026
$10.7MNovel Mechanisms of Exercise Training Effects on Glucose HomeostasisR01DK099511 · NIDDK · JOSLIN DIABETES CENTER · PI LAURIE J GOODYEAR · 2014 to 2026
$6.5MRole of Inflammation-Resolving Lipid Mediators In Ischemic RevascularizationR01HL106173 · NHLBI · UNIVERSITY OF LOUISVILLE · PI SPITE, MATTHEW R · 2011 to 2023
$5.7MRole of BMPs in Adipogenesis, Mitochondrial Function and Energy MetabolismR01DK077097 · NIDDK · JOSLIN DIABETES CENTER · PI TSENG, YU-HUA · 2007 to 2019
$5.6MFibroblast Growth Factor and Energy MetabolismR01DK102898 · NIDDK · JOSLIN DIABETES CENTER · PI TSENG, YU-HUA · 2015 to 2024
$4.1MThe Lipidomics of Adipose Tissue ThermogenesisK01DK111714 · NIDDK · MAINEHEALTH · PI LYNES, MATTHEW D · 2017 to 2021
$804kNovel 12/15 lipoxygenase inhibitors for the treatment of strokeR21NS087165 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI VAN LEYEN, KLAUS · 2014 to 2015
$576kRole of resolvins in macrophage-mediated tissue repairF32HL136044 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SANSBURY, BRIAN EDWARD · 2017 to 2019
$190kTelomerase as a Marker of Brown and White Adipose Tissue Stem CellsF32DK102320 · NIDDK · JOSLIN DIABETES CENTER · PI LYNES, MATTHEW D · 2014 to 2014
$53kNHLBI NIH HHS F32 HL136044NHLBI NIH HHS R01 HL106173NIDDK NIH HHS F32 DK102320NIDDK NIH HHS K01 DK111714NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK077097NIDDK NIH HHS R01 DK082659NIDDK NIH HHS R01 DK099511NIDDK NIH HHS R01 DK102898NIDDK NIH HHS T32 DK007260NIGMS NIH HHS P01 GM095467NINDS NIH HHS R21 NS087165
Abstract
Distinct oxygenases and their oxylipin products have been shown to participate in thermogenesis by mediating physiological adaptations required to sustain body temperature. Since the role of the lipoxygenase (LOX) family in cold adaptation remains elusive, we aimed to investigate whether, and how, LOX activity is required for cold adaptation and to identify LOX-derived lipid mediators that could serve as putative cold mimetics with therapeutic potential to combat diabetes. By utilizing mass-spectrometry-based lipidomics in mice and humans, we demonstrated that cold and β3-adrenergic stimulation could promote the biosynthesis and release of 12-LOX metabolites from brown adipose tissue (BAT). Moreover, 12-LOX ablation in mouse brown adipocytes impaired glucose uptake and metabolism, resulting in blunted adaptation to the cold in vivo. The cold-induced 12-LOX product 12-HEPE was found to be a batokine that improves glucose metabolism by promoting glucose uptake into adipocytes and skeletal muscle through activation of an insulin-like intracellular signaling pathway.
Indexed as
Adipocytes, BrownAdipose Tissue, BrownAnimalsArachidonate 12-LipoxygenaseCell LineCold-Shock ResponseEnergy MetabolismFemaleGlucoseHumansMaleMiceObesityThermogenesisAlox12b protein, mouseALOX12 protein, humanArachidonate 12-LipoxygenaseGlucose12-HEPEadipocytesbrown adipose tissuediabeteseicosapentaenoic acidfatlipidomiclipokineobesitythermogenesis
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