Recurrent restriction of sleep and inadequate recuperation induce both adaptive changes and pathological outcomes

Abstract

Chronic restriction of a basic biological need induces adaptations to help meet requisites for survival. The adaptations to chronic restriction of sleep are unknown. A single episode of 10 days of partial sleep loss in rats previously was shown to be tolerated and to result in increased food intake and loss of body weight as principal signs. The purpose of the present experiment was to investigate the extent to which adaptation to chronic sleep restriction would ameliorate short-term effects and result in a changed internal phenotype. Rats were studied during 10 wk of multiple periods of restricted and unrestricted sleep to allow adaptive changes to develop. Control rats received the same ambulatory requirements only consolidated into periods that lessened interruptions of their sleep. The results indicate a latent period of relatively stable food and water intake without weight gain, followed by a dynamic phase marked by enormous increases in food and water intake and progressive loss of body weight, without malabsorption of calories. Severe consequences ensued, marked especially by changes to the connective tissues, and became fatal for two individuals. The most striking changes to internal organs in sleep-restricted rats included lengthening of the small intestine, decreased size of adipocytes, and increased incidence of multilocular adipocytes. Major organs accounted for an increased proportion of total body mass. These changes to internal tissues appear adaptive in response to high energy production, decomposition of lipids, and increased need to absorb nutrients, but ultimately insufficient to compensate for inadequate sleep.

Fig. 1.

Schematic representation of the experimental periods. After 7 days of recovery from surgery and 7 days of baseline monitoring, rats were either restricted of sleep or served as ambulation controls. Each tick mark represents 1 day. During 10-day sleep-restriction periods, subject sleep was fragmented and reduced in amount. During 10-day ambulation periods, subjects were administered an ambulatory requirement equivalent in total time to that of the sleep-restricted group but consolidated to increase undisturbed sleep opportunities. Each 10-day period of sleep restriction or ambulation was followed by 2 days of recovery in each group (■), during which sleep was permitted near ad libitum.

Fig. 2.

Representative histological images of multilocular and unilocular adipocytes. Left: A section of adipose tissue from the perirenal depot in a chronically sleep-restricted rat illustrative of heterogeneity of the morphology and prevalence of multilocular adipocytes in some regions. Multilocular regions are clusters of notably small yet relatively uniformly sized lipid droplets encased within a single membrane. Right: section of adipose tissue from the perirenal depot of an ambulation-control rat showing a unilocular phenotype with a comparatively homogeneous cell size. Stained with hematoxylin and eosin. Bar = 50 μm.

Fig. 3.

The effect of chronically inadequate sleep on water and food intake and body weight. Percent change from baseline daily values for water intake (top), food intake (middle), and body weight (bottom), across 6 cycles of sleep restriction and sleep recovery in sleep-restricted rats (■) and across 6 cycles of ambulation requirements and sleep recovery in ambulation-control rats (○). Recovery periods are indicated by the white vertical bars. Values are means (SE). n = 10 per group.

Fig. 4.

Representative frequency distribution of adipocyte size in chronically sleep-restricted and ambulation-control rats. Bars represent the number of adipocytes standardized to 0.5 mm² of retroperitoneal adipose tissue, tallied in size intervals of 200 μm², from ambulation control (n = 10) and sleep-restricted (n = 8) rats. Values are means ± SE.