Flattened Circadian Glucocorticoid Oscillations Cause Obesity Due to Increased Lipid Turnover and Lipid Uptake

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


Manuscript in revision for eLife; currently in bioRxiv