Kisspeptin and energy balance in reproduction

Abstract

Kisspeptin is vital for the neuroendocrine regulation of GNRH secretion. Kisspeptin neurons are now recognized as a central pathway responsible for conveying key homeostatic information to GNRH neurons. This pathway is likely to mediate the well-established link between energy balance and reproductive function. Thus, in states of severely altered energy balance (either negative or positive), fertility is compromised, as is Kiss1 expression in the arcuate nucleus. A number of metabolic modulators have been proposed as regulators of kisspeptin neurons including leptin, ghrelin, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY). Whether these regulate kisspeptin neurons directly or indirectly will be discussed. Moreover, whether the stimulatory role of leptin on reproduction is mediated by kisspeptin directly will be questioned. Furthermore, in addition to being expressed in GNRH neurons, the kisspeptin receptor (Kiss1r) is also expressed in other areas of the brain, as well as in the periphery, suggesting alternative roles for kisspeptin signaling outside of reproduction. Interestingly, kisspeptin neurons are anatomically linked to, and can directly excite, anorexigenic POMC neurons and indirectly inhibit orexigenic NPY neurons. Thus, kisspeptin may have a direct role in regulating energy balance. Although data from Kiss1r knockout and WT mice found no differences in body weight, recent data indicate that kisspeptin may still play a role in food intake and glucose homeostasis. Thus, in addition to regulating reproduction, and mediating the effect of energy balance on reproductive function, kisspeptin signaling may also be a direct regulator of metabolism.

The impact of adipose tissue-derived factors on the hypothalamic-pituitary-gonadal (HPG) axis

“…[41][42][43][44] Kisspeptin levels are suppressed by food restriction, as for instance a 72 h fast, which may explain the disruption of the reproductive axis during a negative energy balance. Kisspeptin has no effect of its own on energy balance.…”

Kisspeptin antagonist prevents RF9-induced reproductive changes in female rats

“…Kisspeptin neurons are relatively well known to mediate metabolic effects on reproductive status (De Bond & Smith 2014, Roa & Tena-Sempere 2014. Adult female mice lacking kisspeptin signaling (kiss1r KO) displayed dramatically higher body weight (Tolson et al 2014), which also suggests that kisspeptin signaling also plays a reciprocal role in regulating energy and metabolic status.…”

The Content of Thyroid Hormone Receptor α in Ewe Kisspeptin Neurones is not Season‐Dependent

“…For example, in SD maintained hamsters, hypothalamic T3 implants quickly induced (within 1 week) a significant increase in weight lasting over the subsequent 10 weeks (31). Because Kiss neurones, in addition to promoting the success of seasonal reproduction, are also key integrators of metabolic signals mediated by interneurones involved in food intake such as pro-opiomelanocortin (POMC) neurones and neuropeptide Y (NPY) neurones (41), THRa available in Kiss neurones could participate in this metabolic regulation.…”