ArticleMolecular and cellular biology2014
12-lipoxygenase promotes obesity-induced oxidative stress in pancreatic islets.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- 12-Lipoxygenase (12-LOX) plays a key role in the hyperinflammatory response caused by SARS-CoV-2.mBio · 2026Article
- 12-Lipoxygenase Inhibition Improves Glycemia and Obesity-associated Inflammation in Male Human Gene Replacement Mice.Endocrinology · 2025Article
- Deuterium trafficking, mitochondrial dysfunction, copper homeostasis, and neurodegenerative disease.Frontiers in molecular biosciences · 2025Review
- 12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice.JCI insight · 2024Article
- Adipose Tissue-Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15-HETE Production and Inhibiting AMPK Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- 12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice.bioRxiv : the preprint server for biology · 2024Article
- Tempol, a Superoxide Dismutase Mimetic, Inhibits Wallerian Degeneration Following Spinal Cord Injury by Preventing Glutathione Depletion and Aldose Reductase Activation.Journal of neurotrauma · 2024Article
- Bioactive lipid regulation of platelet function, hemostasis, and thrombosis.Pharmacology & therapeutics · 2023Review
- Molecular Changes in Cells of Patients with Type 2 Diabetes Mellitus Depending on Changes in Glycemia Level in the Context of Lifestyle-An Overview of the Latest Scientific Discoveries.Current issues in molecular biology · 2023Review
- Male infertility and somatic health - insights into lipid damage as a mechanistic link.Nature reviews. Urology · 2022Review
- Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis.Endocrinology · 2022Review
- Effects of Inflammatory Factor Expression Regulated by 12/15 Lipoxygenase on Obesity-Related Nephropathy.Nutrients · 2022Article
- Proinflammatory signaling in islet β cells propagates invasion of pathogenic immune cells in autoimmune diabetes.Cell reports · 2022Article
- Review
- Review
- β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances.Metabolites · 2021Review
- 12-Lipoxygenase governs the innate immune pathogenesis of islet inflammation and autoimmune diabetes.JCI insight · 2021Article
- Regulation of Tissue Inflammation by 12-Lipoxygenases.Biomolecules · 2021Review
- Phenotypic sexual dimorphism in response to dietary fat manipulation in C57BL/6J mice.Journal of diabetes and its complications · 2021Article
- Worldwide flavor enhancer monosodium glutamate combined with high lipid diet provokes metabolic alterations and systemic anomalies: An overview.Toxicology reports · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
High-fat diets lead to obesity, inflammation, and dysglycemia. 12-Lipoxygenase (12-LO) is activated by high-fat diets and catalyzes the oxygenation of cellular arachidonic acid to form proinflammatory intermediates. We hypothesized that 12-LO in the pancreatic islet is sufficient to cause dysglycemia in the setting of high-fat feeding. To test this, we generated pancreas-specific 12-LO knockout mice and studied their metabolic and molecular adaptations to high-fat diets. Whereas knockout mice and control littermates displayed identical weight gain, body fat distribution, and macrophage infiltration into fat, knockout mice exhibited greater adaptive islet hyperplasia, improved insulin secretion, and complete protection from dysglycemia. At the molecular level, 12-LO deletion resulted in increases in islet antioxidant enzymes Sod1 and Gpx1 in response to high-fat feeding. The absence or inhibition of 12-LO led to increases in nuclear Nrf2, a transcription factor responsible for activation of genes encoding antioxidant enzymes. Our data reveal a novel pathway in which islet 12-LO suppresses antioxidant enzymes and prevents the adaptive islet responses in the setting of high-fat diets.
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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.