Flattened circadian glucocorticoid oscillations cause obesity due to increased lipid turnover and lipid uptake

Chronic stressors flatten circadian glucocorticoid oscillations, which has been correlated with negative health outcomes including obesity. How flatter circadian glucocorticoid oscillations affect metabolism and fat storage remains unknown. Here we aimed to investigate the consequences of flattened glucocorticoid oscillations in mice. We found that flattening glucocorticoid oscillations not only results in body weight gain mainly due to an increase in white fat depot mass, but also leads to fat accumulation in brown adipose tissue and to hyperinsulinemia. A transcriptomic analysis of white and brown adipose tissues revealed that flattened glucocorticoid oscillations resulted in a dysregulated lipid metabolism with a prominent role of Cd36. Indeed, Cd36 knockout mice are partially protected against body weight gain and lipid accumulation in the brown and visceral white fat depots induced by flattened glucocorticoid oscillations. These results provide insights how conditions associated with flattened glucocorticoid levels cause obesity.