Fig. 9
From: Sexually dimorphic metabolic responses mediated by CRF2 receptor during nutritional stress in mice
Stress receptor CRF2 dysregulation exacerbates metabolic outcomes of acute dietary stress. Acute or short-term fatty food consumption perturbs function in multiple target organs, including liver, pancreas, and fat depots, collectively, these manifested symptoms constitute metabolic syndrome and diabetes. One compensatory mechanism is to increase CRF2 receptor expression/function in the liver and other target tissues in order to bring function back to homeostasis. If stressors are removed, function can return to homeostasis (black arrows), but chronic stress exposure may ultimately result in frank metabolic syndrome. Dysregulated CRF2 receptor function (as in Crhr2−/− mice) compromises metabolic function even in absence of nutritional stress and puts one on a trajectory to develop metabolic syndrome and diabetes, with males at a greater risk than females. Chronic stress, including consumption of fat- or calorie-rich diets worsens metabolic functions. Thus, CRF2 receptor is a sexually dimorphic risk factor for development of metabolic syndrome and associated diseases such as type 2 diabetes