ArticleProstaglandins & other lipid mediators2021
20-HETE interferes with insulin signaling and contributes to obesity-driven insulin resistance.
Article in Prostaglandins & other lipid mediators, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Enriched Marine Oil Supplement Increases Specific Plasma Specialized Pro-Resolving Mediators in Adults with Obesity.The Journal of nutrition · 2022Trial
- GPR75 in glutamatergic neurons regulates body weight.Cell reports · 2026Article
- Gpr75 Deletion in Adipocytes Protects From Diet-Induced Obesity: Changes in Glucose Homeostasis and Inflammatory Responses.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Neuronal GPR75 deficiency protects against diet-induced obesity in a humanized mouse model.Science advances · 2026Article
- Orphan GPCRs in diabetes mellitus: metabolic control, inflammation, and drug development.Frontiers in endocrinology · 2026Review
- GPR75 signaling is dispensable for reproduction but contributes to feeding and body growth in rats on normal chow and is involved in high-fat diet-induced hyperphagia, obesity, and hyperglycemia development.Endocrine journal · 2025Article
- Integrated screening identifies GPR31 as a key driver and druggable target for metabolic dysfunction-associated steatohepatitis.The Journal of clinical investigation · 2025Article
- Arachidonic acid metabolism in metabolic dysfunction-associated steatotic liver disease and liver fibrosis.Hepatology communications · 2025Review
- Simvastatin inhibits 20-Hydroxyeicosatetraenoic acid formation: docking and in vitro assay.BMC pharmacology & toxicology · 2025Article
- GPR75: Advances, Challenges in Deorphanization, and Potential as a Novel Drug Target for Disease Treatment.International journal of molecular sciences · 2025Review
- Central regulation of feeding and body weight by ciliary GPR75.The Journal of clinical investigation · 2024Article
- Effect and mechanism of GPR75 in metabolic dysfunction-related steatosis liver disease.International journal of medical sciences · 2024Review
- The Synergistic and Opposing Roles of ω-Fatty Acid Hydroxylase (Genome biology & molecular genetics · 2024Article
- Association of Maternal Diet with Infant Birthweight in Women with Gestational Diabetes Mellitus.Nutrients · 2023Article
- Mice deficient for G-protein-coupled receptor 75 display altered presynaptic structural protein expression and disrupted fear conditioning recall.Journal of neurochemistry · 2023Article
- G Protein-Coupled Receptor 75 (GPR75) As a Novel Molecule for Targeted Therapy of Cancer and Metabolic Syndrome.Asian Pacific journal of cancer prevention : APJCP · 2023Review
- Gpr75-deficient mice are protected from high-fat diet-induced obesity.Obesity (Silver Spring, Md.) · 2023Article
- Bioactive oxylipins in type 2 diabetes mellitus patients with and without hypertriglyceridemia.Frontiers in endocrinology · 2023Article
- Determination of Lipoxygenase, CYP450, and Non-Enzymatic Metabolites of Arachidonic Acid in Essential Hypertension and Type 2 Diabetes.Metabolites · 2022Article
- Birth Weight and Early Postnatal Outcomes: Association with the Cord Blood Lipidome.Nutrients · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
20-HETE, a metabolite of arachidonic acid produced by Cytochrome P450 (CYP) 4A/4 F, has been implicated in the development of obesity-associated complications such as diabetes and insulin resistance. In this study, we examined whether the acute elevation of 20-HETE levels contributes to the development of diet-driven hyperglycemia and insulin resistance. We employed a conditional transgenic mouse model to overexpress Cyp4a12 (Cyp4a12tg), a murine 20-HETE synthase, together with high fat diet (HFD) feeding. Mice in which Cyp4a12 was induced by doxycycline (DOX) at the onset of HFD feeding gained weight at a greater rate and extent than corresponding DOX-untreated Cyp4a12 mice. Cyp4a12tg mice fed HFD + DOX displayed hyperglycemia and impaired glucose metabolism while corresponding HFD-fed Cyp4a12tg mice (no DOX) did not. Importantly, administration of a 20-HETE antagonist, 20-SOLA, to Cyp4a12tg mice fed HFD + DOX significantly attenuated weight gain and prevented the development of hyperglycemia and impaired glucose metabolism. Levels of insulin receptor (IR) phosphorylation at Tyrosine 972 and insulin receptor substrate-1 (IRS1) phosphorylation at serine 307 were markedly decreased and increased, respectively, in liver, skeletal muscle and adipose tissues from Cyp4a12tg mice fed HFD + DOX; 20-SOLA prevented the IR and IRS1 inactivation, suggesting that 20-HETE interferes with insulin signaling. Additional studies in 3T3-1 differentiated adipocytes confirmed that 20-HETE impairs insulin signaling and that its effect may require activation of its receptor GPR75. Taken together, these results provide strong evidence that 20-HETE interferes with insulin function and contributed to diet-driven insulin resistance.
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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.