Shift work cycle-induced alterations of circadian rhythms potentiate the effects of high fat diet on inflammation and metabolism

Based on genetic models with mutation or deletion of core clock genes, circadian disruption has been implicated in the pathophysiology of metabolic disorders. Thus, we examined whether circadian desynchronization in response to shift work–type schedules is sufficient to compromise metabolic homeostasis and whether inflammatory mediators provide a key link in the mechanism by which alterations of circadian timekeeping contribute to diet-induced metabolic dysregulation. In high-fat diet (HFD)-fed mice, exposure to chronic shifts of the light–dark cycle (12 h advance every 5 d): 1) disrupts photoentrainment of circadian behavior and modulates the period of spleen and macrophage clock gene rhythms; 2) potentiates HFD-induced adipose tissue infiltration and activation of proinflammatory M1 macrophages; 3) amplifies macrophage proinflammatory cytokine expression in adipose tissue and bone marrow–derived macrophages; and 4) exacerbates diet-induced increases in body weight, insulin resistance, and glucose intole...