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Evers, S.S.* ; Shao, Y.* ; Ramakrishnan, S.K.* ; Shin, J.H.* ; Bozadjieva-Kramer, N.* ; Irmler, M. ; Stemmer, K. ; Sandoval, D.A.* ; Shah, Y.M.* ; Seeley, R.J.*

Gut HIF2α signaling is increased after VSG, and gut activation of HIF2α decreases weight, improves glucose, and increases GLP-1 secretion.

Cell Rep. 38:110270 (2022)

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Bariatric Surgery ; Glp-1 ; Hypoxia-inducible Factor ; Iron Regulation ; Metabolic Surgery ; Obesity ; Type 2 Diabetes ; Vertical Sleeve Gastrectomy ; Von Hippel Lindau; Vertical Sleeve Gastrectomy; Gastric Bypass-surgery; Bariatric Surgery; Iron-deficiency; Medical Therapy; Homeostasis; Hif-2-alpha; Absorption

ISSN (print) / ISBN 2211-1247

e-ISSN 2211-1247

Journal Cell Reports

Quellenangaben Volume: 38, Issue: 3, Article Number: 110270

Publisher Cell Press

Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Experimental Genetics (IEG)
Institute of Diabetes and Obesity (IDO)

Grants China Scholarship Council (CSC)
Novo Nordisk
'Deutsche Forschungsgemeinschaft (DFG)'
Michigan Diabetes Research Center, University of Michigan
University of Michigan
AstraZeneca
Pfizer
Eli Lilly and Company
National Cancer Institute of the National Institutes of Health (NIH)
MNORC
Helmholtz Alliance
German Center for Diabetes Research (BMBF)
GI Center