Suppression of body weight and eating disorders, such as anorexia, are one of the major symptoms of psychiatric disorders such as depression. However, the mechanisms of weight loss and reduced appetite in depressive patients and in animal models of depression are largely unknown. In this study, we characterized the mechanism of anorexia resulting from depression using socially defeated rats as an animal model of depression. Socially defeated rats showed suppressed body weight gain, enlarged adrenal glands, decreased home cage activity, decreased food intake, and increased immobility in the forced swim test. These results are representative of some of the core symptoms of depression. Simultaneously, we observed decreased levels of phosphorylated AMP-activated protein kinase (AMPK) and acetyl-coenzyme A (CoA) carboxylase (ACC) and increased levels of malonyl-CoA in the hypothalamus of socially defeated rats. Hypothalamic malonyl-CoA controlled feeding behavior and elevation of malonyl-CoA in the hypothalamus induced inhibition of food intake. Our findings suggest that the suppression of body weight gain caused by social defeat stress is caused by anorexic feeding behavior via an increased concentration of malonyl-CoA in the hypothalamus. (C) 2012 Elsevier Inc. All rights reserved.