| First Author | Doig CL | Year | 2017 |
| Journal | Endocrinology | Volume | 158 |
| Issue | 6 | Pages | 1964-1976 |
| PubMed ID | 28368470 | Mgi Jnum | J:245940 |
| Mgi Id | MGI:5914307 | Doi | 10.1210/en.2016-1722 |
| Citation | Doig CL, et al. (2017) 11beta-HSD1 Modulates the Set Point of Brown Adipose Tissue Response to Glucocorticoids in Male Mice. Endocrinology 158(6):1964-1976 |
| abstractText | Glucocorticoids (GCs) are potent regulators of energy metabolism. Chronic GC exposure suppresses brown adipose tissue (BAT) thermogenic capacity in mice, with evidence for a similar effect in humans. Intracellular GC levels are regulated by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity, which can amplify circulating GC concentrations. Therefore, 11beta-HSD1 could modulate the impact of GCs on BAT function. This study investigated how 11beta-HSD1 regulates the molecular architecture of BAT in the context of GC excess and aging. Circulating GC excess was induced in 11beta-HSD1 knockout (KO) and wild-type mice by supplementing drinking water with 100 mug/mL corticosterone, and the effects on molecular markers of BAT function and mitochondrial activity were assessed. Brown adipocyte primary cultures were used to examine cell autonomous consequences of 11beta-HSD1 deficiency. Molecular markers of BAT function were also examined in aged 11beta-HSD1 KO mice to model lifetime GC exposure. BAT 11beta-HSD1 expression and activity were elevated in response to GC excess and with aging. 11beta-HSD1 KO BAT resisted the suppression of uncoupling protein 1 (UCP1) and mitochondrial respiratory chain subunit proteins normally imposed by GC excess. Furthermore, brown adipocytes from 11beta-HSD1 KO mice had elevated basal mitochondrial function and were able to resist GC-mediated repression of activity. BAT from aged 11beta-HSD1 KO mice showed elevated UCP1 protein and mitochondrial content, and a favorable profile of BAT function. These data reveal a novel mechanism in which increased 11beta-HSD1 expression, in the context of GC excess and aging, impairs the molecular and metabolic function of BAT. |
