Stress and Body Weight Regulation

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DESCRIPTION (provided by applicant): The regulation of food intake and body weight is a complex interaction of multiple factors. Among these factors is the social milieu in which the animal lives and in particular the social stress that accompanies dominance hierarchies. We utilize a unique animal model of social stress to study how such social hierarchies influence the regulation of food intake and body weight and additionally to uncover the neuroendocrine mechanisms that underlie social influences on body weight. In particular, we found that when animals are placed into a visible burrow system (VBS), we can identify the subordinate (SUB) and dominant (DOM) animals and that SUB animals have reduced body weight when they are in the burrow. The focus of this proposal is to test several hypotheses concerning the mechanism by which social stress in subordinate animals alters the fundamental neuroendocrine circuits involved in the regulation of food intake and body weight. The proposed experiments are critical to a complete understanding of how food intake and body weight are regulated. Importantly, the proposed model offers a novel approach for exploring the complicated but vital relationship between the stress/HPA system and body weight regulation. Specific Aims are: 1) To determine whether the weight loss that is observed in SUB is a result of reduced energy intake and/or increased energy expenditure. In addition, we will determine several endocrine and neurochemical endpoints that are altered by negative energy balance. With several novel control groups for comparison (dominant rats, ad lib fed, pair-fed and body weight-matched), we will be able to determine which major systems interact to produce the observed body weight changes. 2) To determine whether the reduced food intake and/or increased energy expenditure of SUB is secondary to a homeostatic down regulation of the defended amount of body fat, or to a direct catabolic action of stress hormones and neurotransmitters. 3) To test the hypothesis that multiple cycles of chronic stress in the VBS and recovery will produce more severe and enduring changes in body weight regulatory systems than exposure to a single episode. The health significance of this research is clear. Determining how CNS mechanisms involved in the regulation of energy balance are altered by stress is critical to a complete understanding of the co-morbidity of stress related disease states and obesity. Interestingly both stress and food intake regulation share common neurochemical systems and this proposal attempts to define both the interrelatedness as well as the independence of the mechanisms that govern each system. The execution of this proposal will provide insight into the connections between different levels of this regulatory system and thereby give direction to how multiple interventions might best be used to prevent or treat obesity and associated conditions resulting from stress.