Disruptions in circadian rhythms, the normal timing system of the body, can lead to metabolic disorders and obesity. These disruptions can occur because of altered sleep/wake cycles or changes in scheduled mealtimes. The biological significance of food makes the temporal availability of meals critical for many different behavioral or physiological functions. Humans and other animal species learn to associate food availability with cues in the environment or properties intrinsic to the food. We associate times of the day with eating, so that we are normally eating meals at breakfast, lunch and dinner. Humans and other animal species have learned to expect food at certain times of the day as indicated by preprandial increases in both anticipatory activity (food anticipatory activity;FAA) and peptides/hormones (insulin, ghrelin and glucagon-like peptide-1). Both central and peripheral circadian oscillators appear to be important for driving the behavioral and physiological changes prior to mealtime as indicated from the many knockout mouse models of various circadian clock genes, as well as other studies. It is not clear, though, what mealtime cues actually set the circadian oscillators in rhythm. Although the light/dark cycle is important for setting many circadian rhythms, FAA can be seen when animals are under constant light or constant dark conditions (1, 2). This suggests that meal entrainment cues other than those for the light/dark cycle are important. Intrinsic properties of the food (food metabolites or hormones/peptides released as a result of digestion) may be able to set the circadian oscillators to drive further changes in behavior and physiology. I propose to use a model of meal entrainment in laboratory rats to understand how food interacts with circadian oscillators that are responsible for the timing of expression/release of factors important in metabolism and the development of obesity. This may serve as a useful model for understanding the underlying mechanisms responsible for the increased propensity of metabolic disorders and development of obesity in individuals with altered circadian cycles and for a more broadly based understanding of the neurobiology of circadian rhythms and feeding.

Public Health Relevance

Teasing apart the separate contributions of organ-specific or nuclei-specific oscillators may help in identifying important components in a pathway responsible for metabolic abnormalities, obesity and the increased motivation to eat.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZDK1-GRB-9 (M1))
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Podskalny, Judith M,
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Johns Hopkins University
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Dailey, Megan J; Moghadam, Alexander A; Moran, Timothy H (2014) Nutrient-specific feeding and endocrine effects of jejunal infusions in obese animals. Am J Physiol Regul Integr Comp Physiol 306:R420-8
Dailey, Megan J; Stingl, Katherine C; Moran, Timothy H (2012) Disassociation between preprandial gut peptide release and food-anticipatory activity. Endocrinology 153:132-42
Dailey, Megan J; Kim, Seyun (2012) Inositol polyphosphate multikinase: an emerging player for the central action of AMP-activated protein kinase. Biochem Biophys Res Commun 421:1-3