Epidemiologic data have shown associations between short sleep duration and elevated body mass index (BMI). So far, the major evidence in support of a causal mechanism comes from our laboratory studies of healthy young adults submitted to sleep restriction, showing that short sleep results in altered glucose regulation, decreased leptin levels, increased ghrelin levels, and increased hunger and appetite, suggesting an increased risk of weight gain. The majority of the epidemiologic studies did not control for sleep quality. Yet, many adults who regularly curtail their sleep do not enjoy the sleep quality of healthy young subjects. In particular, reduced sleep quality is typical of normal aging and is highly prevalent in overweight and obese individuals. We have recently obtained important new data demonstrating that experimental reductions of sleep quality without change in sleep duration results in alterations of glucose and appetite regulation that could also lead to an increased risk of obesity. Furthermore, our previous work has shown that decreased sleep quality is an intrinsic consequence of recurrent sleep restriction. These findings indicate that reduced sleep quality may be part of the mechanisms linking short sleep and obesity risk. We therefore propose to obtain causative evidence linking short sleep, either of normal or of impaired quality, to alterations in specific central nervous system and peripheral pathways regulating energy intake. Normal young adults will be studied under 3 controlled laboratory conditions: 5 days (i.e. mimicking one work week) with undisturbed sleep (8.5hrs in bed; "baseline"), 5days with short undisturbed sleep (4.5 hrs in bed; "short sleep") and 5 days of short sleep with experimental fragmentation of NREM sleep (4.5 hrs in bed; "fragmented short sleep"). Both the "short sleep" and "fragmented short sleep" conditions will be followed by 2 nights of undisturbed recovery sleep with 9 hours in bed. The studies will combine brain imaging by PET and fMRI, estimations of sympatho-vagal balance, measurements of orexigenic and anorexigenic factors, cytokines and adipokines, continuous assessment of glucose levels via subcutaneous sensors, in vitro studies of insulin signaling in adipocytes from fat biopsies, and behavioral expression of hunger and food intake. A multi-disciplinary group of expert investigators will collaborate to test the role of specific pathways in the link between short/poor sleep and the increased risk of obesity.

R01HL086459

2006-09-15

2011-06-30