Restricted feeding-induced sleep, activity, and body temperature changes in normal and preproghrelin-deficient mice

Abstract

Behavioral and physiological rhythms can be entrained by daily restricted feeding (RF), indicating the existence of a food-entrainable oscillator (FEO). One manifestation of the presence of FEO is anticipatory activity to regularly scheduled feeding. In the present study, we tested if intact ghrelin signaling is required for FEO function by studying food anticipatory activity (FAA) in preproghrelin knockout (KO) and wild-type (WT) mice. Sleep-wake activity, locomotor activity, body temperature, food intake, and body weight were measured for 12 days in mice on a RF paradigm with food available only for 4 h daily during the light phase. On RF days 1-3, increases in arousal occurred. This response was significantly attenuated in preproghrelin KO mice. There were progressive changes in sleep architecture and body temperature during the subsequent nine RF days. Sleep increased at night and decreased during the light periods while the total daily amount of sleep remained at baseline levels in both KO and WT mice. Body temperature fell during the dark but was elevated during and after feeding in the light. In the premeal hours, anticipatory increases in body temperature, locomotor activity, and wakefulness were present from RF day 6 in both groups. Results indicate that the preproghrelin gene is not required for the manifestation of FAA but suggest a role for ghrelinergic mechanisms in food deprivation-induced arousal in mice.

Vertical ground reaction force measurements and video measurements provide comparable estimates of distance moved by mice during artificial light and dark periods

“…Both of these methods were equally sensitive enough to detect the about 60% difference in mean distance moved during the artificial light period and the dark period. However, typically the activity of mice during the dark period is two to three times higher compared to the activity during the light period (Mount and Willmott, 1967;Dauncey and Brown, 1987;Szentirmai et al, 2010). This somewhat smaller than expected difference in the present study was probably related to the fact that the animals were handled and the housing cage lid was changed just prior to the beginning of the light period measurement, neither of which were done prior to the dark period measurement.…”

“…Specifically we tested whether a video-based tracking is feasible during the dark period. This is because mice are primarily nocturnal animals (Mount and Willmott, 1967;Dauncey and Brown, 1987;Szentirmai et al, 2010), and as done previously (Biesiadecki et al, 1999), we also assessed whether the developed new method can reliably differentiate the activity of mice during the dark period from that during the light period. Since no golden standard exists for measuring distance moved by mice over a long period of time, vertical ground reaction force (GRF) based tracking was used as a reference method to the video analysis.…”

Endocrine regulation of circadian physiology

“…ob/ob mice and Obrbmutant Zucker rats show increased FAA under RF, which can be suppressed by the administration of recombinant leptin (Mistlberger & Marchant 1999, Ribeiro et al 2011. In contrast, ghrelin receptor (Ghsr)-deficient mice show impaired FAA (Blum et al 2009, LeSauter et al 2009, Lamont et al 2014; though intriguingly, ghrelin-deficient mice are normal under these conditions (Szentirmai et al 2010). The mechanisms that mediate leptin and ghrelin effects on FAA remain unknown.…”

Interactions between endocrine and circadian systems

“…Ghrelin administration increases FAA; however, studies on rodents lacking functional ghrelin signalling are contradictory. Mice lacking ghrelin receptors are reported to have dampened FAA (LeSauter et al 2009), whilst mice lacking preproghrelin show intact FAA responses during restricted feeding (RF; Szentirmai et al 2010). Ghrelin can feed back onto the circadian clock by directly affecting clock gene expression in the SCN (Yannielli et al 2007).…”