Endocrine Abstracts

Chronic stress, low socioeconomic status and ingestion of hypercaloric food are all 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 (CPS) in which animals of low social rank (subordinates, SUB) are vulnerable to weight gain while animals of high social rank (dominants, DOM) are resilient. Recent data will be discussed demonstrating that social status and genetic predisposing factors interact with the nutritional environment to establish individual vulnerability to stress-induced metabolic disorders. Firstly we demonstrated that animals exhibiting high rank (DOM) that are hyperactive and show sympathetic hyperactivity, are fully protected from the development of metabolic disorders when fed both a standard and a high fat diet, despite being hyperphagic. Secondly, we demonstrated that SUB mice fed a standard diet exhibited features of MetS and downregulation of the insulin pathway downstream of IRS and PPARs in liver and skeletal muscle as well as complex changes in lipid metabolism facilitating fat deposition and in WAT. Furthermore, exposing wt mice to hypercaloric diet induced the development of glucose intolerance and insulin resistance. Similarly subordination stress aggravated glucose intolerance in the diabetic db/db strain of mice. Overall, we demonstrated a robust stress- and social status-dependent effect on the development of MetS and T2D and provided insights on the underling molecular mechanisms. Our results are reminiscent of, and provide a model for, the effect of the individual socioeconomic status on human health.