| First Author | Morgan RA | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 10633 |
| PubMed ID | 28878267 | Mgi Jnum | J:256366 |
| Mgi Id | MGI:6109036 | Doi | 10.1038/s41598-017-10410-1 |
| Citation | Morgan RA, et al. (2017) Carbonyl reductase 1 catalyzes 20beta-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity. Sci Rep 7(1):10633 |
| abstractText | Carbonyl Reductase 1 (CBR1) is a ubiquitously expressed cytosolic enzyme important in exogenous drug metabolism but the physiological function of which is unknown. Here, we describe a role for CBR1 in metabolism of glucocorticoids. CBR1 catalyzes the NADPH- dependent production of 20beta-dihydrocortisol (20beta-DHF) from cortisol. CBR1 provides the major route of cortisol metabolism in horses and is up-regulated in adipose tissue in obesity in horses, humans and mice. We demonstrate that 20beta-DHF is a weak endogenous agonist of the human glucocorticoid receptor (GR). Pharmacological inhibition of CBR1 in diet-induced obesity in mice results in more marked glucose intolerance with evidence for enhanced hepatic GR signaling. These findings suggest that CBR1 generating 20beta-dihydrocortisol is a novel pathway modulating GR activation and providing enzymatic protection against excessive GR activation in obesity. |
