Adipocyte REVERBα dictates adipose tissue expansion during obesity

The circadian clock component REVERB is considered a dominant regulator of lipid metabolism, with global Reverb deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion (ReverbFlox2-6AdipoCre), and transcriptional profiling demonstrates that, under basal conditions, direct targets of REVERB regulation are limited, and include the circadian clock and collagen dynamics. Under high-fat diet (HFD) feeding, ReverbFlox2-6AdipoCre mice do manifest profound obesity, yet without the accompanying WAT inflammation and fibrosis exhibited by controls. Integration of the WAT REVERB cistrome with differential gene expression reveals broad control of metabolic processes by REVERB which is unmasked in the obese state. Adipocyte REVERB does not drive an anticipatory daily rhythm in WAT lipogenesis, but rather modulates WAT activity in response to alterations in metabolic state. Importantly, REVERB action in adipocytes is critical to the development of obesity-related WAT pathology and insulin resistance.