Social stress is prevalent in many facets of modern society. Epidemiological data suggest that stress is linked to the development of overweight, obesity and metabolic disease. We have established the visible burrow system (VBS) model of chronic social stress in our laboratory. In the VBS, mixed gender colonies of rats are housed for 2-week periods during which male rats of the colony quickly develop a dominance hierarchy resulting in subordinate (SUB) and dominant (DOM) animals. We found that SUB animals have reduced body weight during social stress. With repeated, intermittent exposures to social stress in the VBS followed by periods of recovery, SUB rats progressively develop characteristics of obesity that occur, in part, through neuroendocrine alterations and changes in food intake, and predispose the animals to develop other symptoms of the metabolic syndrome. Thus, the VBS model offers a naturalistic paradigm for rigorously examining causal factors that enhance (or diminish) the interaction of social stress with metabolic regulation, while also allowing sophisticated analyses of the control systems involved. We are therefore proposing to continue using the VBS with the following three specific aims.
Specific aims are: 1.) To test the hypothesis that SUB have improved glucose tolerance despite having greater adiposity following repeated cycles of chronic social stress and recovery, and that this is due in part to increased glucose removal from the blood;and that this in turn is secondary to altered expression of glucose transporters (GLUT) in key tissues. We further hypothesize that over a long-term recovery period following the final cycle of social stress, SUB will become more obese and revert to worsened glucose tolerance, 2.) To test the hypothesis that diet composition, macronutrient availability, or meal patterns, or a combination of these parameters, alters the metabolic consequences of social stress. Specifically, increased dietary fat is hypothesized to exacerbate the tendency for SUB to regain body weight preferentially as visceral adipose tissue during recovery from the VBS. Endocrine and neuropeptide mediators of stress and energy homeostasis will be determined in response to dietary manipulations prior to, during, and after episodes of social stress, 3) determine whether genetic susceptibility to diet-induced obesity affects the behavioral, neuroendocrine, neuropeptide, and metabolic consequences resulting from social stress. This collection of studies have direct human significance in understanding how chronic stress and recovery from stress affects changes in behavior, physiology, and metabolism associated with obesity and its associated metabolic disorders.

Public Health Relevance

Social stress is prevalent in many facets of modern society and a well documented consequence of social stress is the development of obesity. We have developed a laboratory model, the visible burrow system (VBS), to study the effects of social stress in rodents in which we find that during recovery from repeated bouts of social stress, rats develop symptoms of metabolic syndrome similar to those observed in humans such as altered endocrine measures and increased visceral adiposity. Using this naturalistic model allows study of interactions between social stress and metabolism, thereby providing insight toward therapies used to treat and prevent obesity and related diseases in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK066596-08
Application #
8099699
Study Section
Special Emphasis Panel (ZRG1-IFCN-A (02))
Program Officer
Yanovski, Susan Z
Project Start
2004-01-01
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
8
Fiscal Year
2011
Total Cost
$320,889
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
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
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
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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