A Central Circadian Clock-Adipose Tissue Circuit Regulates Thermogenesis and Energy Balance

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PROJECT SUMMARY Disruption of circadian rhythms is strongly correlated to obesity and metabolic diseases. Mice with a dysfunctional clock and individuals who experience shift work, jet lag, and sleep disorders develop glucose intolerance, insulin resistance, and weight gain. Recent data indicates the timing of food consumption is a key determinant of metabolic health. Mice and humans in constant darkness have a disrupted diurnal rhythm of diet-induced thermogenesis (DIT). Furthermore, our lab has found that isocaloric feeding in mice during the light period results in pronounced weight gain and glucose intolerance, as compared to the dark period. This effect of differential weight gain during the light vs dark period is lost in mice lacking adipose tissue thermogenesis. This suggests adipose tissue thermogenesis is regulated in a circadian manner to align DIT with optimal feeding times (dark period in mice). However, the mechanisms that integrate adipose tissue thermogenesis with feeding remain unclear. In this proposal, we aim to characterize the central circadian control of adipose tissue sympathetic stimulation and thermogenic activation. The experiments in this proposal will reveal a novel neurocircuit that aligns feeding rhythms with adipose tissue DIT to maintain energy homeostasis.