Hormonal controls of obesity in feeding and fasting hibernating mammals
Date
2010
Authors
Healy, Jessica, author
Florant, Gregory L., advisor
Kanatous, Shane B., 1968-, advisor
Ghalambor, Cameron K., committee member
Irlbeck, Nancy A., committee member
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Abstract
Mammals that hibernate (hibernators) are intriguing models for the study of controls of food intake and adiposity due to their robust circannual cycle of obesity and anorexia. The pathways controlling these cycles in hibernators have not been fully elucidated. In order to clarify the relationships between various hormones, enzymes and metabolic factors, I examined endogenous and experimentally manipulated levels of several factors in hibernators kept under various physiological conditions, including short-term fasting in summer, long-term fasting in winter, and at low and high body temperature. I compared orexigenic factors (such as the hormone ghrelin and the enzyme AMP-activated protein kinase (AMPK)) with anorexigenic compounds (such as leptin and the enzyme acetyl CoA carboxylase (ACC)) at various times of the year and under experimentally manipulated conditions. Ghrelin is an orexigenic hormone produced by the stomach which increases food intake. Leptin is an anorexigenic hormone produced by white adipose tissue (WAT) which decreases food intake. Both of these hormones impact AMPK, a cellular-energy sensing enzyme that increases food intake and fatty acid oxidation through its inactivation of ACC. I found distinct seasonal profiles of these enzymes and hormones that correlated well with the observed life history characteristics of one species of hibernator, the golden-mantled ground squirrel (GMGS, Callospermophilus lateralis). In spring and summer, when GMGS are normophagic and lipogenic, the hormone profile of hibernators was much like non-hibernating rodents--AMPK and ghrelin increased with fasting, and injected ghrelin caused an increase in food intake with an associated increase in the active form of AMPK (pAMPK). In autumn, when GMGS are hyperphagic and lipogenic, circulating ghrelin concentrations were higher than at other times of the year, and release of leptin from WAT lagged behind fat mass to allow hyperphagic animals to become obese before hibernation. In winter, when GMGS were aphagic and lipolytic, AMPK and ACC activation were higher in torpid than in euthermic animals, circulating leptin concentrations were once again coupled with fat mass, ghrelin was still circulating in the blood, but at lower concentrations than during normophagic seasons, and circulating ghrelin was higher in euthermic than in torpid GMGS. This was the first published investigation of the hormone ghrelin in a true hibernator, and provides a potential explanation of the dramatic seasonal changes in food intake seen in mammals that hibernate.
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Subject
AMPK
leptin
hibernation
ghrelin
food intake
Golden-mantled ground squirrel -- Hibernation
Hibernation -- Endocrine aspects
Ghrelin
Leptin
Obesity in animals