Cell ReportsArticleGlucocorticoid-Induced ObesityDevelops Independently of UCP1

Ineke H.N. Luijten, Katie Brooks, Nathalie Boulet, Irina G. Shabalina, Ankita Jaiprakash, Bo Carlsson, Alexander W. Fischer, Barbara Cannon, and Jan Nedergaard


An excess of glucocorticoids leads to the develop-ment of obesity in both mice and humans, but themechanism for this is unknown. Here, we determinethe extent to which decreased BAT thermogenic ca-pacity (as a result of glucocorticoid treatment) con-tributes to the development of obesity. Contrary toprevious suggestions, we show that only in micehoused at thermoneutrality (30C) does corticoste-rone treatment reduce total BAT UCP1 protein. Thisreduction is reflected in reduced brown adipocytecellular and mitochondrial UCP1-dependent respira-tion. However, glucocorticoid-induced obesity de-velops to the same extent in animals housed at21C and 30C, whereas total BAT UCP1 proteinlevels differ 100-fold between the two groups.In corticosterone-treated wild-type and UCP1knockout mice housed at 30C, obesity also de-velops to the same extent. Thus, our results demon-strate that the development of glucocorticoid-induced obesity is not caused by a decreasedUCP1-dependent thermogenic capacity.