ArticleNature medicine2017
Activation of intestinal hypoxia-inducible factor 2α during obesity contributes to hepatic steatosis.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- Impact of exercise training in a hypobaric/normobaric hypoxic environment on body composition and glycolipid metabolism in individuals with overweight or obesity: a systematic review and meta-analysis.Frontiers in physiology · 2025Pooled it
- Divergent Hypoxia-Inducible Factor 2‑Alpha Signaling in Alcoholic Liver Disease and Metabolic Dysfunction-Associated Steatotic Liver Disease.ACS pharmacology & translational science · 2026Review
- Hepatic HIF2α Modulates Extra-Hepatic Disease-Associated Phenotypes During Metabolic Dysfunction-Associated Steatotic Liver Disease.Comprehensive physiology · 2026Article
- Understanding the role of hypoxia inducible factors in liver fibrosis and future therapeutic applications.iLIVER · 2026Review
- UBE2M deficiency in alveolar macrophages promotes emphysema through HIF-2α/MMP12 axis.Chinese medical journal pulmonary and critical care medicine · 2026Article
- How the gut microbiome affects the immunotherapy response in hepatocellular carcinoma.Cancer biology & medicine · 2026Review
- A Somatic Mutation in HIF-2α Affects Glucose and Lipid Metabolism via CD36 and Ceramide.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Hypoxia-inducible factors in the immunometabolism of metabolic dysfunction-associated steatotic liver disease (MASLD): molecular mechanisms and therapeutic implications.Frontiers in physiology · 2026Article
- Hypoxia-inducible factors link inflammation and lipid metabolism in atherosclerotic macrophages.Frontiers in cardiovascular medicine · 2026Review
- Therapeutic nutrition strategies for the shared pathophysiology of obesity and sleep-disordered breathings.Nutrition journal · 2025Review
- Ubiquitination of TFEB increased intestinal permeability to aggravate metabolic dysfunction-associated steatohepatitis.Hepatology (Baltimore, Md.) · 2025Article
- Hypoxia-inducible factor 2α overexpression in podocytes ameliorates lipid metabolism disorders in diabetic kidney disease by inhibiting S1P.Renal failure · 2025Article
- Article
- The Emerging Role of Sialic Acids in Obesity and Diabetes: Molecular Mechanisms and Therapeutic Perspectives.Biomolecules · 2025Review
- Microbial riboflavin inhibits ceramide synthase 3 to lower ceramide (d18:1/26:0) and delay colorectal cancer progression.Cell metabolism · 2025Article
- Chronic cerebral hypoperfusion induces venous dysfunction via EPAS1 regulation in mice.Nature communications · 2025Article
- Orchestration of Gut-Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation.Biomedicines · 2025Review
- Iron Replacement Attenuates Hypoxic Pulmonary Hypertension by Remodeling Energy Metabolism via Regulating the HIF2α/Mitochondrial Complex I, III/ROS Axis.Biomolecules · 2025Article
- The carotenoid torularhodin alleviates NAFLD by promoting Akkermanisa muniniphila-mediated adenosylcobalamin metabolism.Nature communications · 2025Article
- Comprehensive microarray analysis for the identification of therapeutic targets within HIF-1α signalling networks in diet-induced obesity via hypothalamic inflammation.Archives of endocrinology and metabolism · 2025Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Nonalcoholic fatty liver disease is becoming the most common chronic liver disease in Western countries, and limited therapeutic options are available. Here we uncovered a role for intestinal hypoxia-inducible factor (HIF) in hepatic steatosis. Human-intestine biopsies from individuals with or without obesity revealed that intestinal HIF-2α signaling was positively correlated with body-mass index and hepatic toxicity. The causality of this correlation was verified in mice with an intestine-specific disruption of Hif2a, in which high-fat-diet-induced hepatic steatosis and obesity were substantially lower as compared to control mice. PT2385, a HIF-2α-specific inhibitor, had preventive and therapeutic effects on metabolic disorders that were dependent on intestine HIF-2α. Intestine HIF-2α inhibition markedly reduced intestine and serum ceramide levels. Mechanistically, intestine HIF-2α regulates ceramide metabolism mainly from the salvage pathway, by positively regulating the expression of Neu3, the gene encoding neuraminidase 3. These results suggest that intestinal HIF-2α could be a viable target for hepatic steatosis therapy.
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