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

Author
item SZENTIRMAI, EVA - Washington State University
item KAPAS, LEVENTE - Washington State University
item SUN, YUXIANG - Children'S Nutrition Research Center (CNRC)
item SMITH, ROY - Scripps Institute
item KRUEGER, JAMES - Washington State University

Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/24/2009
Publication Date: 2/1/2010
Citation: Szentirmai, E., Kapas, L., Sun, Y., Smith, R.G., Krueger, J.M. 2010. Restricted feeding-induced sleep, activity, and body temperature changes in normal and preproghrelin-deficient mice. American Journal of Physiology. 298:R467-R477.

Interpretive Summary: Food is critical for all living beings. When food is restricted to a few hours per day, animals exhibit anticipatory activity before mealtime (food-anticipatory activity). Evidence suggests that this anticipation is caused by a food-entrainable oscillator (FEO). However, the mechanism of how food entrainment occurs is unclear. In the present study, we tested whether ghrelin signaling is required for FEO function by studying food-anticipatory activity in normal mice and in ghrelin gene-deleted mice. Results indicate that the preproghrelin gene is not required for the manifestation of food anticipatory activity, but suggest that ghrelin may have a role in food deprivation-induced arousal in mice. Additional studies will be accomplished to better understand the role of ghrelin.

Technical 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.