Mechanism controlling sleep organization of the obese Zucker rats

Abstract

We tested the hypothesis that the obese (fa/fa) Zucker rat has a sleep organization that differs from that of lean Zucker rats. We used the polygraphic technique to identify and to quantify the distribution of the three main states of the rat: wakefulness (W), non-rapid-eye-movement (NREM), and rapid-eye movement (REM) sleep states. Assessment of states was made with light present (1000-1600), at the rats thermoneutral temperature of 29 degrees C. Obese rats, compared with lean ones, did not show significant differences in the total time spent in the three main states. Whereas the mean durations of W and REM states did not differ statistically, that of NREM did (P = 0.046). However, in the obese rats, the frequencies of switching from NREM sleep to W, which increased, and from NREM to REM sleep, which decreased, were statistically significantly different (P = 0.019). Frequency of switching from either REM or W state was not significantly different. We conclude that sleep organization differs between lean and obese Zucker rats and that it is due to a disparity in switching from NREM sleep to either W or REM sleep and the mean duration of NREM sleep.

Sleep and obesity: A focus on animal models

“…Recent epidemiological and animal studies supported these earlier observations and showed a crucial interplay between sleep and body weight regulation (Danguir, 1989; Guan et al, 2008; Jenkins et al, 2006; Kalra et al, 2008; Laposky et al, 2006; Liu et al, 2008; Megirian et al, 1998; Rao et al, 2009; Vgontzas et al, 2008). While it was recognized that 7–8 hours of uninterrupted sleep was optimal for adults, the reliance on self-reported sleep rather than objective measures (Marshall et al, 2008) has led to discrepancies in the literature focused on the relationship between sleep time and obesity, which has been extensively reviewed (Cappuccio et al, 2008; Marshall et al, 2008; Nielsen et al, 2011; Patel et al, 2008).…”

“…Some models show deficient leptin or orexin signaling similar to obese individuals and narcoleptic patients (Beck et al, 2001; Laposky et al, 2006; Megirian et al, 1998; Sanchez-Alavez et al, 2007; Tschop and Heiman, 2001; Zhang et al, 2007), but unlike human obesity, obesity in several models results from a single gene deficiency. Sleep architecture in these animal models resemble the abnormalities observed in human obesity (excessive sleep, specifically during the active phase; sleep fragmentation; decreased REM sleep during the resting phase).…”

Circadian Clocks and Metabolism

“…Reduced sleep duration (both acute and chronic) and poor-quality sleep are linked with impaired glucose tolerance, reduced insulin responsiveness following glucose challenge, increased body mass index, decreased levels of leptin, and increased levels of ghrelin (Donga et al 2010; Gottlieb et al 2005; Knutson and Van Cauter 2008; Megirian et al 1998; Nilsson et al 2004; Spiegel et al 2009; Taheri et al 2004). Association studies have further revealed that shift workers have increased risk of obesity, metabolic dysfunction, cardiovascular disease, cancer, and ischemic stroke (Di Lorenzo et al 2003; Ellingsen et al 2007; Karlsson et al 2001, 2003).…”

Leptin: A biomarker for sleep disorders?

“…A role of leptin in sleep regulation is shown by its ability to decrease REM sleep and increase slow wave sleep [67]. However, leptin is not the main driving factor for increased total sleep time and NREM sleep in obesity, as seen in mice fed with a high-fat diet [68], ob/ob mice lacking leptin [40,41] and obese Zucker rats with defective ObR [69,70]. …”