Chronic stress and adipose tissue in the anorexic state: endocrine and epigenetic mechanisms

Although adipose tissue metabolism in obesity has been widely studied, there is limited research on the anorexic state, where the endocrine system is disrupted by reduced adipose tissue mass and there are depot-specific changes in adipocyte type and function. Stress exposure at different stages of life can alter the balance between energy intake and expenditure and thereby contribute to the pathogenesis of anorexia nervosa. This review integrates information from human clinical trials to describe endocrine, genetic and epigenetic aspects of adipose tissue physiology in the anorexic condition. Changes in the hypothalamus-pituitary-thyroid, -adrenal, and -gonadal axes and their relationships to appetite regulation and adipocyte function are discussed. Because of the role of stress in triggering or magnifying anorexia, and the dynamic but also persistent nature of environmentally-induced epigenetic modifications, epigenetics is likely the link between stress and long-term changes in the endocrine system that disrupt homoeostatic food intake and adipose tissue metabolism. Herein, we focus on the adipocyte and changes in its function, including alterations reinforced by endocrine disturbance and dysfunctional adipokine regulation. This information is critical because of the poor understanding of anorexic pathophysiology, due to the lack of suitable research models, and the complexity of genetic and environmental interactions.