Energy Expenditure is Affected by Rate of Accumulation of Sleep Deficit in Rats

INSUFFICIENT AND DISRUPTED SLEEP IS WIDESPREAD IN WESTERN SOCIETY. SLEEP DISTURBANCES AND DISORDERS MAY AFFECT UP TO ONE THIRD of the population1 and have been linked to the metabolic syndrome,2,3 a cluster of pathologies including obesity, hypertension, and type 2 diabetes, which affects up to 40% of adults in America.4 Growing evidence suggests that chronic sleep debt may play a causal role in the development of disease in otherwise-healthy individuals and may exacerbate the progression of preexisting illness.5 However, it remains unclear whether short sleep in humans is of real clinical significance because weight gain is often minimal even in chronic short sleepers.6 Long-term interventional studies are needed to investigate possible causal links among sleep quantity, sleep quality, and energy balance, but such studies are logistically and ethically problematic in human subjects. Animal models of chronic sleep loss may provide insight into these issues. Extensive studies of prolonged sleep deprivation in rats have identified a broad spectrum of pathophysiologic outcomes.7 In an extensive series of studies of total sleep deprivation (TSD) using the disk over water (DOW) technique, Rechtschaffen and colleagues7 noted a consistent metabolic response that developed in rats, including an increase in total daily energy expenditure to approximately twice the baseline level.8 In their study, food intake was increased to 80% above baseline, yet body weight declined, indicating a profoundly negative energy balance despite hyperphagia.8 Prolonged deprivation of (mainly) rapid eye movement (REM) sleep in rats—using both the DOW9 and platform techniques—has also led to progressively increased metabolic rate and negative energy balance.10 That TSD induces a negative energy balance in rats is in stark contrast with the documented correlation between short sleep and obesity in human populations.11 Although the above animal studies of prolonged sleep deprivation have contributed substantially to our understanding of the physiologic consequences of acute sleep debt, they have only limited relevance to most individuals in today's society who complain of sleep problems but nevertheless obtain at least some daily sleep.1 Yet, the physiologic consequences of chronic sleep restriction (CSR, also known as chronic partial sleep deprivation) remain poorly understood. Recent studies indicate that the development of a chronic sleep debt may be associated with adaptive responses that are not apparent during acute sleep deprivation12; McEwan13 has proposed that chronic sleep debt of sufficient severity may impose an allostatic load on multiple physiologic systems. It is unknown whether energy metabolism adapts to a chronic sleep debt, but such an effect may provide insight into the contrasting energy-balance responses in rats and humans. A recent study of chronic sleep fragmentation in rats challenged with dietary sodium cholate provides indirect support for this hypothesis.14 Van Dongen and colleagues have defined the term sleep debt as “the increased pressure for sleep that results from an inadequate amount of physiologically normal sleep.”15 Unfortunately it is not yet clear how much sleep is needed to satisfy functional demand (so-called “core sleep”),16 especially in nonhuman animals. We therefore use the term sleep deficit in this paper to represent a reduction in sleep below resting baseline levels to acknowledge uncertainty in the extent to which this represents a reduction below physiologic sleep requirement in rats. The results of the present study provide the first tentative estimate of core sleep time in rats. Here we tested the hypothesis that responses in whole-body energy metabolism (measured indirectly as rate of oxygen uptake, O2) and body temperature (Tb) vary with the rate of accumulation of sleep deficit by comparing these responses in rats under conditions of prolonged TSD and CSR.