Biology Reference
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Thus, conditions of long-term obesity in adulthood have been associated to
some degree of suppression of the hypothalamic Kiss1 system. This contention
was initially suggested by our studies in diet-induced obese male mice of the
C57/B6 strain (
Luque et al., 2007
), and was later documented by subsequent
analyses in DBA/2J mice, which are prone to develop obesity-induced infer-
tility (
Tortoriello, McMinn, & Chua, 2004
), in which diet-induced obesity
caused a significant suppression of kisspeptin expression in the ARC and
RP3V of females (
Quennell et al., 2011
). On the other hand, early-onset obe-
sitymight cause opposite effects on the hypothalamic Kiss1 system, at least dur-
ing puberty, as we have recently documented that postnatal overfeeding of
female rats induces earlier occurrence of puberty in association with increased
hypothalamic expression of
Kiss1
and a trend for higher numbers of kisspeptin
fibers in the RP3V immediately prior the onset of puberty (
Castellano et al.,
2011
). Admittedly, however, the magnitude of these changes seems modest
and other studies in rats and mice have failed to detect clear-cut changes in
hypothalamic Kiss1 expression following postnatal over-nutrition (
Caron,
Ciofi, Prevot, & Bouret, 2012; Smith & Spencer, 2012
); a discrepancy that
might be due to differences in the methodological approaches, age-windows
of analysis and species used among those studies. In any event, the sensitivity
of the developing Kiss1 system to early metabolic influences is stressed by find-
ings in undernourished rats and mice during the postnatal period that display
indices of suppression of the hypothalamic Kiss1 system, namely decreased
Kiss1
expression and kisspeptin-positive neurons/fibers, coupled to delayed
puberty (
Caron et al., 2012; Castellano et al., 2011
).
In this context, the possibility that metabolic signals may act directly on
Kiss1 neurons has been actively investigated. Again, most of the attention
on this front has concentrated primarily on leptin. Yet, direct or indirect evi-
dence for the potential actions of ghrelin and insulin onKiss1 neurons has also
been reported (
Forbes, Li, Kinsey-Jones, &O'Byrne, 2009; Qiu et al., 2013
).
Regarding leptin effects, the detectable expression of the mRNA encoding
the functional leptin receptor, LepRb (also termedOb-Rb), at least in a subset
of Kiss1 neurons in the ARC, as documented in the mouse and sheep
(
Backholer et al., 2010; Smith et al., 2006
), and the capacity of leptin, at least
at high doses, to enhance the hypothalamic expression of
Kiss1
gene in dif-
ferent models of severe metabolic stress, such as the leptin-deficient ob/ob
mouse and the diabetic rat, led to the proposal that leptin acts directly onKiss1
neurons to conduct at least part of its stimulatory/permissive effects onGnRH
neurons (
Castellano Navarro, Fernandez-Fernandez, Roa, et al., 2006;
Luque et al., 2007; Smith et al., 2006
). This possibility is further supported
