Journal
PSYCHONEUROENDOCRINOLOGY
Volume 38, Issue 12, Pages 2933-2942Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.psyneuen.2013.07.022
Keywords
Social stress; Dominance; Subiordination; Type 2 diabetes; Laptin; Adiponectin; Glucose tolerance test; Hyperphagia
Categories
Funding
- University of Parma
- MMF
- UofMN Medical School
- MRC
- MRC DU
- Cambridge Phenomics Centre
- Medical Research Council [MC_G0802535, MC_UU_12012/2, G0600717, MC_UU_12012/5/B, G0802051, G0600717B] Funding Source: researchfish
- MRC [G0600717, MC_G0802535, G0802051, MC_UU_12012/2] Funding Source: UKRI
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Stress and hypercaloric food are recognized risk factors for obesity, Metabolic Syndrome (MetS) and Type 2 Diabetes (T2D). Given the complexity of these metabolic processes and the unavailability of animal models, there is poor understanding of their underlying mechanisms. We established a model of chronic psychosocial stress in which subordinate mice are vulnerable to weight gain while dominant mice are resilient. Subordinate mice fed a standard diet showed marked hyperphagia, high leptin, low adiponectin, and dyslipidemia. Despite these molecular signatures of MetS and T2D, subordinate mice fed a standard diet were still euglycemic. We hypothesized that stress predisposes subordinate mice to develop T2D when synergizing with other risk factors. High fat diet aggravated dyslipidemia and the MetS thus causing a pre-diabetes-like state in subordinate mice. Contrary to subordinates, dominant mice were fully protected from stress-induced metabolic disorders when fed both a standard- and a high fat-diet. Dominant mice showed a hyperphagic response that was similar to subordinate but, unlike subordinates, showed a significant increase in VO2, VCO2, and respiratory exchange ratio when compared to control mice. Overall, we demonstrated a robust stress- and social status-dependent effect on the development of MetS and T2D and provided insights on the physiological mechanisms. Our results are reminiscent of the effect of the individual socioeconomic status on human health and provide an animal model to study the underlying molecular mechanisms. (C) 2013 Elsevier Ltd. All rights reserved.
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