Insulin and Leptin Signaling Interact in the Mouse Kiss1 Neuron during the Peripubertal Period.
Insulin and Leptin Signaling Interact in the Mouse Kiss1 Neuron during the Peripubertal Period.
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DOI：
10.1371/journal.pone.0121974
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hill JW
中科院分区：
文献类型：
--
作者：
Qiu X;Dao H;Wang M;Heston A;Garcia KM;Sangal A;Dowling AR;Faulkner LD;Molitor SC;Elias CF;Hill JW
Reproduction requires adequate energy stores for parents and offspring to survive. Kiss1 neurons, which are essential for fertility, have the potential to serve as the central sensors of metabolic factors that signal to the reproductive axis the presence of stored calories. Paradoxically, obesity is often accompanied by infertility. Despite excess circulating levels of insulin and leptin, obese individuals exhibit resistance to both metabolic factors in many neuron types. Thus, resistance to insulin or leptin in Kiss1 neurons could lead to infertility. Single deletion of the receptors for either insulin or the adipokine leptin from Kiss1 neurons does not impair adult reproductive dysfunction. However, insulin and leptin signaling pathways may interact in such a way as to obscure their individual functions. We hypothesized that in the presence of genetic or obesity-induced concurrent insulin and leptin resistance, Kiss1 neurons would be unable to maintain reproductive function. We therefore induced a chronic hyperinsulinemic and hyperleptinemic state in mice lacking insulin receptors in Kiss1 neurons through high fat feeding and examined the impact on fertility. In an additional, genetic model, we ablated both leptin and insulin signaling in Kiss1 neurons (IR/LepRKiss mice). Counter to our hypothesis, we found that the addition of leptin insensitivity did not alter the reproductive phenotype of IRKiss mice. We also found that weight gain, body composition, glucose and insulin tolerance were normal in mice of both genders. Nonetheless, leptin and insulin receptor deletion altered pubertal timing as well as LH and FSH levels in mid-puberty in a reciprocal manner. Our results confirm that Kiss1 neurons do not directly mediate the critical role that insulin and leptin play in reproduction. However, during puberty kisspeptin neurons may experience a critical window of susceptibility to the influence of metabolic factors that can modify the onset of fertility.
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影响因子：
82.9
作者：
Altarejos, Judith Y.;Goebel, Naomi;Conkright, Michael D.;Inotiel, Hiroshi;Xie, Jianxin;Arias, Carlos M.;Sawchenko, Paul E.;Montminy, Marc
通讯作者：
Montminy, Marc
影响因子：
29
作者：
Al-Qassab H;Smith MA;Irvine EE;Guillermet-Guibert J;Claret M;Choudhury AI;Selman C;Piipari K;Clements M;Lingard S;Chandarana K;Bell JD;Barsh GS;Smith AJ;Batterham RL;Ashford ML;Vanhaesebroeck B;Withers DJ
通讯作者：
Withers DJ
DOI：
10.1073/pnas.1834399100
发表时间：
2003-09-16
影响因子：
11.1
作者：
de Roux, N;Genin, E;Milgrom, E
通讯作者：
Milgrom, E
DOI：
10.1002/cne.23032
发表时间：
2012-07-01
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Bosch MA;Xue C;Rønnekleiv OK
通讯作者：
Rønnekleiv OK
影响因子：
4.8
作者：
Barash, IA;Cheung, CC;Steiner, RA
通讯作者：
Steiner, RA