Insulin, leptin, and food reward: update 2008

Abstract

The hormones insulin and leptin have been demonstrated to act in the central nervous system (CNS) as regulators of energy homeostasis at medial hypothalamic sites. In a previous review, we described new research demonstrating that, in addition to these direct homeostatic actions at the hypothalamus, CNS circuitry that subserves reward and motivation is also a direct and an indirect target for insulin and leptin action. Specifically, insulin and leptin can decrease food reward behaviors and modulate the function of neurotransmitter systems and neural circuitry that mediate food reward, i.e., midbrain dopamine and opioidergic pathways. Here we summarize new behavioral, systems, and cellular evidence in support of this hypothesis and in the context of research into the homeostatic roles of both hormones in the CNS. We discuss some current issues in the field that should provide additional insight into this hypothetical model. 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.

Figures

Fig. 1.

Energy regulatory (gray) and reward circuitry (rose) and major synaptic connections. Green labels highlight targets of insulin and leptin; blue labels highlight targets of insulin (not determined for leptin). CNS, central nervous system; PPTN, pedunculopontine tegmental nucleus; PVN, paraventricular nucleus; PF, prefrontal; VTA, ventral tegmental area; SNC substantia nigra pars compacta; NAcc, nucleus accumbens; LH, lateral hypothalamus; ARC, arcuate nucleus.

Fig. 2.

Food intake, energy regulatory, and reward circuitry. Magenta labels highlight CNS sites in which opioid administration stimulates food intake. PBN, parabrachial nucleus; NTS, solitary tract nucleus.