Repeated Exposure to Severely Limited Sleep Results in Distinctive and Persistent Physiological Imbalances in Rats

Abstract

Chronic sleep disruption in laboratory rats leads to increased energy expenditure, connective tissue abnormalities, and increased weights of major organs relative to body weight. Here we report on expanded findings and the extent to which abnormalities become long-lasting, potentially permanent changes to health status after apparent recuperation from chronic sleep disruption. Rats were exposed 6 times to long periods of disrupted sleep or control conditions during 10 weeks to produce adaptations and then were permitted nearly 4 months of undisturbed sleep. Measurements were made in tissues from these groups and in preserved tissue from the experimental and control groups of an antecedent study that lacked a lengthy recuperation period. Cycles of sleep restriction resulted in energy deficiency marked by a progressive course of hyperphagia and major (15%) weight loss. Analyses of tissue composition in chronically sleep-restricted rats indicated that protein and lipid amounts in internal organs were largely spared, while adipose tissue depots appeared depleted. This suggests high metabolic demands may have preserved the size of the vital organs relative to expectations of severe energy deficiency alone. Low plasma corticosterone and leptin concentrations appear to reflect low substrate availability and diminished adiposity. After nearly 4 months of recuperation, sleep-restricted rats were consuming 20% more food and 35% more water than did comparison control rats, despite normalized weight, normalized adipocytes, and elevated plasma leptin concentrations. Plasma cholesterol levels in recuperated sleep-restricted rats were diminished relative to those of controls. The chronically increased intake of nutriments and water, along with altered negative feedback regulation and substrate use, indicate that internal processes are modified long after a severe period of prolonged and insufficient sleep has ended.

Effects of recovery sleep after one work week of mild sleep restriction on interleukin-6 and cortisol secretion and daytime sleepiness and performance

“…These critical questions emphasize the need for future prolonged naturalistic field studies in humans. Notably, recent experiments in animals showed that repeated sleep restriction/ recovery cycles resulted in energy deficiency as shown by hyperphagia and significant weight loss and decreased plasma corticosterone and leptin concentrations as a consequence of diminished adiposity (12,13). Some of these changes were still present even after a 4-mo-long recuperation period, suggesting that repeated sleep restriction/recovery cycles may have lasting effects, which in turn may increase the likelihood of various diseases (13).…”

Impact of insufficient sleep on total daily energy expenditure, food intake, and weight gain

“…Thus, insufficient sleep per se may not directly lead to weight gain and findings from nonhuman models support the latter. Specifically, sleep-restricted rodents lost weight even though they ate more (24) and rats with sleep disturbance because of ventrolateral preoptic area of the hypothalamus lesions (25) gained less weight even though they ate normal amounts of food. Although EE was not directly measured in the latter rodent studies, the findings are consistent with the physiological principal that energy needs are higher during sleep loss.…”

Leptin: A biomarker for sleep disorders?

“…In a study spanning 72 d, rats underwent six cycles of 10 d sleep fragmentation by platform rotation followed by two days of recovery. The decrease of leptin was not significantly different even though there was weight loss [42]. …”