AgRP neurons: The foes of reproduction in leptin-deficient obese subjects

Abstract

E volutionarily, the ability to regulate energy balance and reproduction in parallel is critical, because reproductive success will only occur when sufficient energy supplies are available. In periods when energy stores are depleted, reproduction is switched off in an attempt to save energy to optimize survival for subsequent reproductive success. The cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. In PNAS, Wu et al. (1) shed light on a previously unsuspected neuronal population that appears to be fundamental for the coupling of energy deficit with impaired reproduction. Energy Availability and ReproductionTo perpetuate the species, individuals must maintain an adequate energy balance, which will ultimately allow reproduction. The proper energy homeostasis must be sensed by the whole body to promote the proper endocrine and behavioral switches in support of reproductive success. One mechanism by which the organism transmits information about energy stores is through circulating leptin. Leptin is released by the adipose tissue, and its levels are proportional to the amount of fat (2, 3). Increased leptin levels feed back to tissues to decrease energy intake and deposition and to increase energy expenditure. In such situations, reproduction is the best to occur, because energy is then available to develop a new organism. On the other hand, during depleted energy states (e.g., fasting, malnutrition) that lead to fat depletion, leptin levels are low and reproduction is turned off. One of the phenotypes of chronic fasting or malnutrition is hypothalamic hypogonadism, which is promptly reversed on recovery of energy stores.