Enhanced thermogenesis depends on the circadian clock of adipocytes, study reveals

Mice that eat during the active phase of their daily circadian cycle burn more calories through enhanced thermogenesis, mitigating the development of obesity, researchers report. The findings help explain the mechanisms underlying the benefits of time-restricted feeding and how circadian disruption can contribute to metabolic disease.

While previous studies have shown that the timing of feeding relative to daily circadian cycles of activity and sleep can contribute to the development of obesity and other metabolic maladies, the mechanisms involved remain unknown. To help elucidate these details, Chelsea Hepler and colleagues evaluated the effect of time-restricted feeding (TRF) on mice fed high-fat diets (HFD). Through a series of experiments, Hepler et al. found that when mice were fed a HFD during the active phase of their daily circadian cycle – at night as mice are nocturnal – they burned more calories through adipocyte thermogenesis, which protected them from diet-induced obesity.

The findings reveal that this enhanced thermogenesis depends on the circadian clock of adipocytes and a futile creatine cycle. In mouse models with diminished adipocyte creatine levels, thermogenesis could not be enhanced when feeding was synched to the active phase, resulting in similar weight gain as mistimed feeding.

“TRF in humans appears to be a promising approach to decrease body weight and improve metabolic health with few side effects,” write Damien Lagarde and Lawrence Kazak in a related Perspective. “The work of Hepler et al. expands our knowledge about the mechanisms that underlie the benefits of TRF.”