The corticotropin-releasing hormone system in the regulation of energy balance in obesity.

Abstract

The view that energy balance is regulated has gained acceptance in recent years. An important role in this regulation is played by brain circuitries involved in the control of energy intake (food intake) and energy expenditure (thermogenesis) that are capable of integrating peripheral signals, produced by perturbations of adipose tissue mass, into messages to effectors of food intake and energy expenditure, so as to prevent substantial variations in the level of energy reserves. More than one neurosystem has been reported to genuinely participate in the regulation of energy balance. Among them is the corticotropin-releasing hormone (CRH) system. This system, with its numerous clusters of brain neurons, its closely related peptide urocortin, its two receptor types and its binding protein, all generally widely distributed throughout the brain, forms a network of neuronal pathways capable of interacting with the circuitries controlling food intake and energy expenditure. In addition, CRH and urocortin's anorectic and thermogenic actions appear to be coordinated to optimize energy losses. Finally, the CRH system seems to demonstrate a certain degree of plasticity in obesity and in response to food deprivation that is consistent with its action on food intake and thermogenesis. The observations have been made that food deprivation and obesity can blunt the expression of the CRH type 2alpha receptor in the ventromedial hypothalamic nucleus and can induce the expression of the CRH-binding protein (a CRH-inactivating protein) in brain areas involved in the anorectic and thermogenic actions of CRH.