ArticleJCI insight2022
Adipocyte-derived PGE2 is required for intermittent fasting-induced Treg proliferation and improvement of insulin sensitivity.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Exercise, Prostaglandin ECells · 2026Review
- Periodic fasting and refeeding re-shapes lipid saturation, storage, and distribution in brown adipose tissue.PLoS biology · 2026Article
- Adipose Inositol Monophosphate Metabolism Is Associated with Fasting Regimen-Elicited Metabolic Benefits.Biomolecules · 2025Article
- Article
- Acoustic modulation of mechanosensitive genes and adipocyte differentiation.Communications biology · 2025Article
- Intermittent fasting reduces inflammation and joint damage in a murine model of rheumatoid arthritis: insights from transcriptomic and metagenomic analyses.BMC rheumatology · 2024Article
- Oxylipins Derived from PUFAs in Cardiometabolic Diseases: Mechanism of Actions and Possible Nutritional Interactions.Nutrients · 2024Review
- Uncovering the Role of Selenite and Selenium Nanoparticles (SeNPs) in Adolescent Rat Adipose Tissue beyond Oxidative Balance: Transcriptomic Analysis.Antioxidants (Basel, Switzerland) · 2024Article
- Epigenetic regulation of human FOXP3+ Tregs: from homeostasis maintenance to pathogen defense.Frontiers in immunology · 2024Review
- Depletion of JunB increases adipocyte thermogenic capacity and ameliorates diet-induced insulin resistance.Nature metabolism · 2024Article
- Adipose tissue-derived lipokines in metabolism.Current opinion in genetics & development · 2023Review
- Physiological Approaches Targeting Cellular and Mitochondrial Pathways Underlying Adipose Organ Senescence.International journal of molecular sciences · 2023Review
- Harnessing prostaglandin ETrends in immunology · 2023Review
- Targeting metabolic pathways: a novel therapeutic direction for type 2 diabetes.Frontiers in cellular and infection microbiology · 2023Article
- Article
- Potential benefits of metformin and pioglitazone combination therapy via gut microbiota and metabolites in high-fat diet-fed mice.Frontiers in pharmacology · 2022Article
- A Bibliometric and Visualization Analysis of Intermittent Fasting.Frontiers in public health · 2022Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
The intermittent fasting (IF) diet has profound benefits for diabetes prevention. However, the precise mechanisms underlying IF's beneficial effects remain poorly defined. Here, we show that the expression levels of cyclooxygenase-2 (COX-2), an enzyme that produces prostaglandins, are suppressed in white adipose tissue (WAT) of obese humans. In addition, the expression of COX-2 in WAT is markedly upregulated by IF in obese mice. Adipocyte-specific depletion of COX-2 led to reduced fractions of CD4+Foxp3+ Tregs and a substantial decrease in the frequency of CD206+ macrophages, an increase in the abundance of γδT cells in WAT under normal chow diet conditions, and attenuation of IF-induced antiinflammatory and insulin-sensitizing effects, despite a similar antiobesity effect in obese mice. Mechanistically, adipocyte-derived prostaglandin E2 (PGE2) promoted Treg proliferation through the CaMKII pathway in vitro and rescued Treg populations in adipose tissue in COX-2-deficient mice. Ultimately, inactivation of Tregs by neutralizing anti-CD25 diminished IF-elicited antiinflammatory and insulin-sensitizing effects, and PGE2 restored the beneficial effects of IF in COX-2-KO mice. Collectively, our study reveals that adipocyte COX-2 is a key regulator of Treg proliferation and that adipocyte-derived PGE2 is essential for IF-elicited type 2 immune response and metabolic benefits.
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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.