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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK066596-04
Application #
7161344
Study Section
Special Emphasis Panel (ZRG1-IFCN-4 (94))
Program Officer
Yanovski, Susan Z
Project Start
2004-01-01
Project End
2008-06-30
Budget Start
2007-01-01
Budget End
2008-06-30
Support Year
4
Fiscal Year
2007
Total Cost
$320,201
Indirect Cost
Name
University of Cincinnati
Department
Psychiatry
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Melhorn, Susan J; Elfers, Clinton T; Scott, Karen A et al. (2017) A closer look at the subordinate population within the visible burrow system. Physiol Behav 178:110-116
Boersma, Gretha J; Smeltzer, Michael D; Scott, Karen A et al. (2017) Stress coping style does not determine social status, but influences the consequences of social subordination stress. Physiol Behav 178:126-133
Scott, Karen A; de Kloet, Annette D; Smeltzer, Michael D et al. (2017) Susceptibility or resilience? Prenatal stress predisposes male rats to social subordination, but facilitates adaptation to subordinate status. Physiol Behav 178:117-125
McEwen, Bruce S; McKittrick, Christina R; Tamashiro, Kellie L K et al. (2015) The brain on stress: Insight from studies using the Visible Burrow System. Physiol Behav 146:47-56
Tamashiro, Kellie L K (2015) Developmental and environmental influences on physiology and behavior--2014 Alan N. Epstein Research Award. Physiol Behav 152:508-15
Smeltzer, Michael; Scott, Karen; Melhorn, Susan et al. (2012) Amylin blunts hyperphagia and reduces weight and fat gain during recovery in socially stressed rats. Am J Physiol Regul Integr Comp Physiol 303:R676-82
Scott, Karen A; Melhorn, Susan J; Sakai, Randall R (2012) Effects of Chronic Social Stress on Obesity. Curr Obes Rep 1:16-25
Tamashiro, Kellie L K (2011) Metabolic syndrome: links to social stress and socioeconomic status. Ann N Y Acad Sci 1231:46-55
Krause, Eric G; de Kloet, Annette D; Flak, Jonathan N et al. (2011) Hydration state controls stress responsiveness and social behavior. J Neurosci 31:5470-6
Solomon, Matia B; Sakai, Randall R; Woods, Stephen C et al. (2011) Differential effects of glucocorticoids on energy homeostasis in Syrian hamsters. Am J Physiol Endocrinol Metab 301:E307-16

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