Late effects of sleep restriction: Potentiating weight gain and insulin resistance arising from a high-fat diet in mice

Objective Epidemiological studies show the association of sleep restriction (SR) with obesity and insulin resistance. Experimental studies are limited to the concurrent or short-term effects of SR. Here, we examined the late effects of SR regarding weight gain and metabolic alterations induced by a high-fat diet (HFD). Methods C57BL/6 mice were subjected to a multiple platform method of SR for 15 days, 21 h daily, followed by 6 weeks of a 30% HFD. Results Just after SR, serum insulin and resistin concentrations were increased and glycerol content decreased. In addition, resistin, TNF-α, and IL-6 mRNA expression were notably increased in epididymal fat. At the end of the HFD period, mice previously submitted to SR gained more weight (32.3±1.0 vs. 29.4±0.7 g) with increased subcutaneous fat mass, had increments in the expression of the adipogenic genes PPARγ, C/EBPα, and C/EBPβ, and had macrophage infiltration in the epididymal adipose tissue. Furthermore, enhanced glucose tolerance and insulin resistance were also observed. Conclusions The consequences of SR may last for a long period, characterizing SR as a predisposing factor for weight gain and insulin resistance. Metabolic changes during SR seem to prime adipose tissue, aggravating the harmful effects of diet-induced obesity.