| First Author | Evers SS | Year | 2022 |
| Journal | Cell Rep | Volume | 38 |
| Issue | 3 | Pages | 110270 |
| PubMed ID | 35045308 | Mgi Jnum | J:327100 |
| Mgi Id | MGI:6879578 | Doi | 10.1016/j.celrep.2021.110270 |
| Citation | Evers SS, et al. (2022) Gut HIF2alpha signaling is increased after VSG, and gut activation of HIF2alpha decreases weight, improves glucose, and increases GLP-1 secretion. Cell Rep 38(3):110270 |
| abstractText | 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 HIF2alpha, 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 HIF2alpha 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 HIF2alpha signaling in regulating crosstalk between iron-regulatory systems and other aspects of systemic physiology important for metabolic regulation. |
