ArticleCell reports2022
Gut HIF2α signaling is increased after VSG, and gut activation of HIF2α decreases weight, improves glucose, and increases GLP-1 secretion.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Intestinal HIF1α is dispensable for bariatric surgery-mediated metabolic benefits but protects against diet-induced obesity and hepatic steatosis.International journal of obesity (2005) · 2026Article
- Article
- Targeting hepcidin to restore oral iron efficacy after vertical sleeve gastrectomy.Frontiers in nutrition · 2026Article
- Mechanisms through which laparoscopic sleeve gastrectomy mitigates atherosclerosis risk: a focus on visceral adipose tissue.European journal of medical research · 2025Review
- Hypoxia-Induced Signaling in Gut and Liver Pathobiology.Annual review of pathology · 2024Review
- New insights in the mechanisms of weight-loss maintenance: Summary from a Pennington symposium.Obesity (Silver Spring, Md.) · 2023Review
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Hepatic lipid-associated macrophages mediate the beneficial effects of bariatric surgery against MASH.Research square · 2023Article
- Impact of intestinal microenvironments in obesity and bariatric surgery on shaping macrophages.Immunometabolism (Cobham, Surrey) · 2023Review
- Weight versus weight-independent effects of Roux-en-Y gastric bypass on type 2 diabetes.Nature metabolism · 2023Article
- Iron-tracking strategies: Chaperones capture iron in the cytosolic labile iron pool.Frontiers in molecular biosciences · 2023Review
- Vertical sleeve gastrectomy increases duodenal Lactobacillus spp. richness associated with the activation of intestinal HIF2α signaling and metabolic benefits.Molecular metabolism · 2022Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Gastric bypass and vertical sleeve gastrectomy (VSG) remain the most potent and durable treatments for obesity and type 2 diabetes but are also associated with iron deficiency. The transcription factor HIF2α, which regulates iron absorption in the duodenum, increases following these surgeries. Increasing iron levels by means of dietary supplementation or hepatic hepcidin knockdown does not undermine the effects of VSG, indicating that metabolic improvements following VSG are not secondary to lower iron levels. Gut-specific deletion of Vhl results in increased constitutive duodenal HIF2α signaling and produces a profound lean, glucose-tolerant phenotype that mimics key effects of VSG. Interestingly, intestinal Vhl deletion also results in increased intestinal secretion of GLP-1, which is essential for these metabolic benefits. These data demonstrate a role for increased duodenal HIF2α signaling in regulating crosstalk between iron-regulatory systems and other aspects of systemic physiology important for metabolic regulation.
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Registered trials
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