Sleep is increased in mice with obesity induced by high-fat food
Introduction
Obesity and sleep disturbances are two major health problems associated with modern lifestyles, and the incidences of both conditions are still increasing in many countries. Among the adults in the United States, the prevalence of overweight and obesity is about 60% and 30%, respectively [1]. One of the most common complaints of obese patients is excessive daytime sleepiness (EDS), which is also the most frequent complaint in a sleep clinic. Obesity is often associated with sleep-disordered breathing, the latter might contribute to the EDS. However, different groups independently reported that obese humans display objective EDS regardless of the presence of sleep apnea [2], [3], [4]. These findings are consistent with a study of the prevalence of EDS in a large general, randomized sample that suggests that obesity is a significant risk factor for EDS independent of sleep-disordered breathing and age [5].
Recently, a link between sleep duration with obesity is suggested by several studies based on self-report. It has been shown that obesity is associated with bimodal sleep patterns, i.e., some obese patients report short sleep duration whereas others report long sleep duration within a 24-h cycle [6], [7]. It is not clear what is different between the two groups, and what is the cause–effect relationship between sleep duration and obesity.
The possibility that obesity might influence sleep regulation is suggested by the observations that obesity is associated with increased sleep-promoting cytokines, particularly tumor necrosis factor (TNF) and interleukin-6 (IL-6) [2], [8], [9], [10]. TNF in the brain fluctuates with the light–dark cycle in the brain and is involved in both physiological sleep regulation and sleep responses to sleep deprivation [11], [12], [13]. IL-6 levels display clear light–dark cycle in the human blood [13], [14], and in the rat blood, fat tissue and brain [15]. IL-6 levels in the blood increase following total or partial sleep loss in humans [13], [14]. IL-6 induces sleep alterations in humans [16] and rats [17].
Given the clinical importance of sleep alterations in obesity, studies in animal models will be desirable for evaluating the influences of obesity on sleep and mechanisms for EDS. However, such studies have been very limited. Two studies have observed sleep in the Zucker rat, a genetic obesity model, with mixed results [18], [19]. Another study using leptin-deficient mice showed that sleep is significantly increased during the dark period [20]. Since high-fat food is well known to induce obesity [21], [22], to increase sleepiness in humans [23] and to increase sleep-promoting inflammatory cytokines [2], [8], [9], [10], we hypothesized that NREMS will be increased in obesity induced by high-fat food. To test our hypothesis, we determined the sleep patterns in mice during the course of obesity development induced by high-fat food.
Section snippets
Animals
Adult male C57BL/6 mice (6 months of age) were used in the experiment. All experimental protocols used in the experiment were approved by the Institutional Animal Care and Use Committee (IACUC). The animals were implanted with electroencephalogram (EEG) and electromyography (EMG) electrodes. The experiment started after 2 weeks of recovery from the surgery and additional 4 days of adaptation to the recording procedures. Animals were kept individually in the plastic cages at 23 °C room
Food intake and body weight (Fig. 1)
The calories provided by the food were calculated by multiplying the amounts of foods consumed by the animals with the amounts of calories contained in the foods (3.30 kcal/gm for the regular lab chow and 5.29 kcal/gm for the high-fat food) Fig. 1. The amounts of calorie intake were significantly greater in the high-fat group than in the control group [F(1,21) = 18.566, p < 0.001, main effect]. There was a significant treatment and time (weeks) interaction [F(3,63) = 4.222, p < 0.01]. There was no
Discussion
In the present study, wakefulness was reduced and NREMS was increased in a mouse model of obesity throughout the experimental period that lasted 6 weeks. These alterations were more prominent during the dark period. Similarly, sleep is increased in leptin-deficient ob/ob mice during the dark period [20]. Our results are also consistent with observations that obesity is associated with EDS in humans [3], [4], [5]. Therefore, the effects of obesity on sleep are clearly seen during the active
Acknowledgment
Research supported by NIH research grant HL64245.
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