Fig. P1.

Fasting responses regulated by the MC3R. Deletion of MC3-R in mice causes an obesity syndrome with no measurable hyperphagia or hypometabolism. We used MC3-R^−/− and wild-type mice of the same background strain to characterize energy flux in white adipose tissue (WAT) and liver tissue during fasting. We also examined central neuroendocrine responses to fasting, such as the hypothalamic–pituitary–adrenal (HPA) or stress axis. We identified defects in the utilization of energy from fat, in the accumulation of triglycerides in the liver, and in regulation of the HPA axis in the knockout mice. Further analysis showed that MC3-R regulates energy partitioning by controlling autonomic outflow to WAT and adrenal glucocorticoid production, which in turn controls the flow of nonesterified fatty acids (NEFA) from WAT to the liver.