| First Author | Kiefer MF | Year | 2024 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 327 |
| Issue | 2 | Pages | E203-E216 |
| PubMed ID | 38895981 | Mgi Jnum | J:362269 |
| Mgi Id | MGI:7859939 | Doi | 10.1152/ajpendo.00035.2024 |
| Citation | Kiefer MF, et al. (2024) Intestinal retinol saturase is implicated in the development of obesity and epithelial homeostasis upon injury. Am J Physiol Endocrinol Metab 327(2):E203-E216 |
| abstractText | Retinol saturase (RetSat) is an oxidoreductase involved in lipid metabolism and the cellular sensitivity to peroxides. RetSat is highly expressed in metabolic organs like the liver and adipose tissue and its global loss in mice increases body weight and adiposity. The regulation of RetSat expression and its function in the intestine are unexplored. Here, we show that RetSat is present in different segments of the digestive system, localizes to intestinal epithelial cells, and is upregulated by feeding mice high-fat diet (HFD). Intestine-specific RetSat deletion in adult mice did not affect nutrient absorption and energy homeostasis basally, but lowered body weight gain and fat mass of HFD-fed mice, potentially via increasing locomotor activity. Moreover, jejunal expression of genes related to beta-oxidation and cholesterol efflux was decreased, and colonic cholesterol content was reduced upon RetSat deletion. In colitis, which we show to downregulate intestinal RetSat expression in humans and mice, RetSat ablation improved epithelial architecture of the murine colon. Thus, intestinal RetSat expression is regulated by dietary interventions and inflammation, and its loss reduces weight gain upon HFD feeding and alleviates epithelial damage upon injury.NEW & NOTEWORTHY Retinol saturase (RetSat) is an oxidoreductase with unknown function in the intestine. We found that RetSat localizes in intestinal epithelial cells and that its deletion reduced weight gain and fat mass in obese mice. In colitis, which decreased intestinal RetSat expression in humans and mice, RetSat ablation improved the epithelial architecture of the murine colon, presumably by decreasing ROS production, thus rendering RetSat a novel target for metabolic and inflammatory bowel disease. |
