Energy regulatory signals and food reward.

The hormones insulin, leptin, and ghrelin have been demonstrated to act in the central nervous system (CNS) as regulators of energy homeostasis, acting at medial hypothalamic sites. Here, we summarize research demonstrating that, in addition to direct homeostatic actions at the hypothalamus, CNS circuitry that subserves reward and is also a direct and indirect target for the action of these endocrine regulators of energy homeostasis. Specifically, insulin and leptin can decrease food reward behaviors and modulate the function of neurotransmitter systems and neural circuitry that mediate food reward, the midbrain dopamine (DA) and opioidergic pathways. Ghrelin can increase food reward behaviors, and support midbrain DA neuronal function. We summarize discussion of behavioral, systems, and cellular evidence in support of the contributions of reward circuitry to the homeostatic roles of these hormones in the CNS. The understanding of neuroendocrine modulation of food reward, as well as food reward modulation by diet and obesity, may point to new directions for therapeutic approaches to overeating or eating disorders.