Kisspeptin Directly Excites Anorexigenic Proopiomelanocortin Neurons but Inhibits Orexigenic Neuropeptide Y Cells by an Indirect Synaptic Mechanism

Fu, Li-Ying; Pol, Anthony N. van den

doi:10.1523/jneurosci.2098-10.2010

Cited by 207 publications

(206 citation statements)

References 94 publications

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“…There is strong evidence that kisspeptin would decrease food intake and increase energy expenditure, resulting in a decrease in body weight. In one electrophysiological study, kisspeptin has been shown to directly excite POMC/ CART neurons and indirectly inhibit NPY/AgRP neurons (Fu & van den Pol 2010). Our finding that central administration of kisspeptin causes decreases in food intake and body weight is consistent with the results of this Action of RF9 is dependent on kisspeptin signaling electrophysiological study.…”

Section: Central Administration Of P234 Inhibits Kisspeptininduced Fosupporting

confidence: 90%

“…The modulatory effects of RFRP on kisspeptin are important in terms of not only reproductive functions but also nutritional aspects. For example, functional electrophysiological analyses have documented the ability of RFRP-3 to inhibit the excitatory actions of kisspeptins on pro-opiomenalocortin (POMC) neurons (Fu & van den Pol 2010). Therefore, in the present experiment, the importance of the interaction between kisspeptin and RFRP was also investigated in terms of energy metabolism.…”

Section: Introductionmentioning

confidence: 94%

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Kisspeptin antagonist prevents RF9-induced reproductive changes in female rats

et al. 2015

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The aim of this study was to determine the modulatory effects of peptide 234 (p234) (an antagonist of GPR54 receptors) on kisspeptin and RF9 (an RFamide-related peptide antagonist)-induced changes in reproductive functions and energy balance in female rats. Female Sprague-Dawley rats were weaned on postnatal day (pnd) 21. The animals were intracerebroventricularly cannulated under general anesthesia on pnd 23. Groups of female rats were injected with kisspeptin, RF9, p234, kisspeptin plus p234, or RF9 plus p234, daily. The experiments were ended on the day of first diestrus following pnd 60. Kisspeptin or RF9 alone advanced vaginal opening (VO), which was delayed by administration of kisspeptin antagonist alone. In the rats given kisspeptin plus p234 or RF9 plus p234, VO was not different from control rats. Kisspeptin and RF9 elicited significant elevations in circulating LH levels. Coadministrations of kisspeptin or RF9 with p234 decreased LH levels significantly. The use of p234 alone did not cause any significant change in LH secretion. Kisspeptin decreased both food intake and body weight while RF9 decreased only food intake without affecting body weight. The effects of kisspeptin on energy balance were also reversed by central administration of p234. In conclusion, kisspeptin antagonist, p234, modulates the effects of kisspeptin on reproductive functions and energy balance, whereas RF9 seems to exert only its effects on reproductive functions by means of GPR54 signaling in female rats.

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Section: Central Administration Of P234 Inhibits Kisspeptininduced Fosupporting

confidence: 90%

Section: Introductionmentioning

confidence: 94%

Kisspeptin antagonist prevents RF9-induced reproductive changes in female rats

et al. 2015

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“…These neurons may possess Kiss1r because it is expressed in cells within the ARC (Lee et al 1999), which are not kisspeptin neurons . Moreover, electrophysiological recordings in mice show that kisspeptin can directly excite POMC/CART neurons and indirectly inhibit NPY/ AgRP neurons, via a mechanism based on enhancing GABA-mediated inhibitory synaptic tone (Fu & van den Pol 2010). The net effect of such kisspeptin regulation would be to decrease food intake and increase metabolism.…”

Section: Pomc/cart Neuronsmentioning

confidence: 99%

Kisspeptin and energy balance in reproduction

Bond¹,

Smith²

2014

Reproduction

100

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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.

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“…There are neuroanatomical and functional connections between kisspeptin and important hypothalamic appetite‐regulating neuropeptides 15, 16, 17. Intracerebroventricular administration of kisspeptin has been reported to alter food intake in mice18 and chicks,19 while other studies report no effect of kisspeptin administration on appetite in rats 20.…”

Section: Introductionmentioning

confidence: 99%

The effects of kisspeptin on β‐cell function, serum metabolites and appetite in humans

Izzi‐Engbeaya

Comninos

Clarke

et al. 2018

Diabetes Obesity Metabolism

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AimsTo investigate the effect of kisspeptin on glucose‐stimulated insulin secretion and appetite in humans.Materials and methodsIn 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m−2), we compared the effects of 1 nmol kg−1 h−1 kisspeptin versus vehicle administration on glucose‐stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose‐stimulated insulin secretion in vitro in human pancreatic islets and a human β‐cell line (EndoC‐βH1 cells).ResultsKisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose‐stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men.ConclusionsCollectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin‐based therapies for reproductive and potentially metabolic conditions.

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Kisspeptin Directly Excites Anorexigenic Proopiomelanocortin Neurons but Inhibits Orexigenic Neuropeptide Y Cells by an Indirect Synaptic Mechanism

Cited by 207 publications

References 94 publications

Kisspeptin antagonist prevents RF9-induced reproductive changes in female rats

Kisspeptin antagonist prevents RF9-induced reproductive changes in female rats

Kisspeptin and energy balance in reproduction

The effects of kisspeptin on β‐cell function, serum metabolites and appetite in humans

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