ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2016
Intestinal inflammation requires FOXO3 and prostaglandin E2-dependent lipogenesis and elevated lipid droplets.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Chlorogenic acid attenuates LPS-induced hepatic oxidative stress in broilers by regulating cyclooxygenase-2 expression.Poultry science · 2026Article
- Metabolic regulation of gut barrier integrity in IBD: protein, lipid, and carbohydrate pathways.Frontiers in nutrition · 2026Review
- Tumor-Derived Prostaglandin E2 Promotes Colorectal Cancer Progression by Inducing N2-Type TAN Polarization.Cancer science · 2026Article
- The lipid droplet protein Jabba promotes actin remodeling downstream of prostaglandin signaling duringMolecular biology of the cell · 2025Article
- Alterations in gene expression and microbiome composition upon calcium-sensing receptor deletion in the mouse esophagus.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- FOXO3: at the crossroads of metabolic, inflammatory, and tumorigenic remodeling in the colon.American journal of physiology. Gastrointestinal and liver physiology · 2024Review
- FOXO3 Deficiency in Neutrophils Drives Colonic Inflammation and Tumorigenesis.International journal of molecular sciences · 2023Article
- Hermansky-Pudlak syndrome type 1 causes impaired anti-microbial immunity and inflammation due to dysregulated immunometabolism.Mucosal immunology · 2022Article
- Suppression of intestinal dysfunction in a Drosophila model of Parkinson's disease is neuroprotective.Nature aging · 2022Article
- FOXO3 Expression in Macrophages Is Lowered by a High-Fat Diet and Regulates Colonic Inflammation and Tumorigenesis.Metabolites · 2022Article
- Elevated ATGL in colon cancer cells and cancer stem cells promotes metabolic and tumorigenic reprogramming reinforced by obesity.Oncogenesis · 2021Article
- Ulcerative colitis immune cell landscapes and differentially expressed gene signatures determine novel regulators and predict clinical response to biologic therapy.Scientific reports · 2021Article
- Immune Cells and Transcriptional Signatures Revealed Novel Regulators and Predict Clinical Response to Biologic Therapy in Ulcerative Colitis.Journal of cellular immunology · 2021Article
- SEIPIN: A Key Factor for Nuclear Lipid Droplet Generation and Lipid Homeostasis.International journal of molecular sciences · 2020Review
- Implications of lipid droplets in lung cancer: Associations with drug resistance.Oncology letters · 2020Review
- Gut microbes effects on host metabolic alterations in health and disease.Gut microbes · 2020Article
- Silicon dioxide nanoparticle exposure affects small intestine function in an in vitro model.Nanotoxicology · 2018Article
- Reduced mitochondrial activity in colonocytes facilitates AMPKα2-dependent inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Intestinal inflammation has been recently characterized by the dysregulation of lipids as metabolic and energy sources, revealing a novel feature of its pathophysiology. Because intracellular lipids, stored in dynamic lipid droplets (LDs), provide energy for cellular needs, we investigated whether they play a role in intestinal inflammation. In the inflamed intestine of mice, elevated LDs were found in colonic and infiltrating immune cells as shown by staining for the LD coat protein PLIN2 and for lipids with BODIPY. In colonic cells, TNF stimulated LD increases by receptor signaling rely on phosphatidylinositol 3-kinase activation. Downstream, TNF triggered a negative regulatory loop between LDs and the transcription factor FOXO3. This was shown in the colon of Foxo3-deficient mice, where elevation in PLIN2 and lipids were further facilitated by inflammation and were more prominent relative to wild-type, whereas, in colonic cells, inhibition of lipogenesis blocked the TNF-mediated loss of FOXO3. Furthermore, blockade of PGE2 synthesis abrogated TNF-stimulated increases in LDs and FOXO3 inactivation. We found in colonic tissue of Foxo3-deficient mice higher levels of cyclooxygenase-2, a mediator of prostaglandin E2 (PGE2) synthesis, supporting involvement of PGE2 in the LD-FOXO3 regulatory loop. Ultimately, TNF-stimulated lipogenesis leading to elevated LDs facilitated NF-κB-mediated increases in IL-8 protein, which is associated with the surface of LDs found in the lumina of the endoplasmic reticulum and Golgi apparatus. This novel immunometabolic mechanism of colonic inflammation involving elevated LDs could provide opportunities for new treatment options.
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