Chronic sleep fragmentation promotes obesity in young adult mice
Funding agencies: DG is supported by National Institutes of Health grants HL65270 and HL86662. SZ was supported by a Comer Kids Classic grant.
Disclosure: The authors have no competing interests.
Authors Contributions: YW conducted experiments, analyzed data, drafted portions of the manuscript, and served as blinded observer. AC, SXZ, FH, SL, and DN performed experiments and analyzed data. HY performed analyses of metabolic chamber data in a blinded fashion. DG provided the conceptual design of the project, analyzed data, drafted the manuscript, and is responsible for the financial support of the project and the manuscript content. All authors have reviewed and approved the final version of the manuscript. DG is supported by National Institutes of Health grants HL-65270, HL-086662, and HL-107160. Dr. Gozal is the guarantor of this work, had full access to all the data, and takes full responsibility for the integrity of data and the accuracy of data analysis.
Short sleep confers a higher risk of obesity in humans. Restricted sleep increases appetite, promotes higher calorie intake from fat and carbohydrate sources, and induces insulin resistance. However, the effects of fragmented sleep (SF), such as occurs in sleep apnea, on body weight, metabolic rates, and adipose tissue distribution are unknown.
C57BL/6 mice were exposed to SF for 8 weeks. Their body weight, food consumption, and metabolic expenditure were monitored over time, and their plasma leptin levels measured after exposure to SF for 1 day as well as for 2 weeks. In addition, adipose tissue distribution was assessed at the end of the SF exposure using MRI techniques.
Chronic SF-induced obesogenic behaviors and increased weight gain in mice by promoting increased caloric intake without changing caloric expenditure. Plasma leptin levels initially decreased and subsequently increased. Furthermore, increases in both visceral and subcutaneous adipose tissue volumes occurred.
These results suggest that SF, a frequent occurrence in many disorders and more specifically in sleep apnea, is a potent inducer of obesity via activation of obesogenic behaviors and possibly leptin resistance, in the absence of global changes in energy expenditure.