The Emerging Role(s) for Kisspeptin in Metabolism in Mammals.

Andrew Wolfe,Mehboob A Hussain

doi:10.3389/fendo.2018.00184

Andrew Wolfe, Mehboob A Hussain

Open Access

https://doi.org/10.3389/fendo.2018.00184

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Abstract

Kisspeptin was initially identified as a metastasis suppressor. Shortly after the initial discovery, a key physiologic role for kisspeptin emerged in the regulation of fertility, with kisspeptin acting as a neurotransmitter via the kisspeptin receptor, its cognate receptor, to regulate hypothalamic GnRH neurons, thereby affecting pituitary–gonadal function. Recent work has demonstrated a more expansive role for kisspeptin signaling in a variety of organ systems. Kisspeptin has been revealed as a significant player in regulating glucose homeostasis, feeding behavior, body composition as well as cardiac function. The direct impact of kisspeptin on peripheral metabolic tissues has only recently been recognized. Here, we review the emerging endocrine role of kisspeptin in regulating metabolic function. Controversies and current limitations in the field as well as areas of future studies toward kisspeptin’s diverse array of functions will be highlighted.

Highlights

Historical Summary of KisspeptinThe kisspeptin (Kiss1) gene was first identified in a screen of human genes that reduced the metastatic potential of human melanoma cells [1]
To address whether the underlying cause of the obesity in female Kiss1r KO mice was at the level of the hypothalamus, De Bond et al used quantitative PCR and in situ hybridization histochemistry to examine the expression of key genes in the hypothalamic appetite-regulating system, including Pomc and Npy as well as the genes expressing the receptors for leptin, ghrelin, and the melanocortins [79]
These results suggest that liver glucagon receptor activation can both stimulate insulin secretion by increasing blood glucose levels and inhibit insulin secretion by stimulating kisspeptin production

Summary

INTRODUCTION

The kisspeptin (Kiss1) gene was first identified in a screen of human genes that reduced the metastatic potential of human melanoma cells [1]. To address whether the underlying cause of the obesity in female Kiss1r KO mice was at the level of the hypothalamus, De Bond et al used quantitative PCR and in situ hybridization histochemistry to examine the expression of key genes in the hypothalamic appetite-regulating system, including Pomc and Npy as well as the genes expressing the receptors for leptin, ghrelin, and the melanocortins [79] They established that there were no differences in the expression of any of these genes between ovariectomized Kiss1r KO and ovariectomized control mice, suggesting peripheral sites of action of kisspeptin as potentially being a primary contributor to altered metabolism in the Kiss1r KO mouse. To explore kisspeptin’s effects in fat, 3T3-L1 and primary rat hepatocytes were treated with Kp10 and lipid metabolism, glucose uptake and leptin and adiponectin secretion assessed [101] These studies demonstrated that Kp10 reduced adipogenesis in 3T3-L1 cells, likely as a result of a reduced expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) and CCAAT/ enhancer binding protein beta (CEBPβ), transcription factors involved in stimulating adipogenesis. Leveraging conditional knockout mouse models of both kisspeptin and the KISS1R will be required to fully understand kisspeptin’s role in regulating heart contractility and gut motility

Summary and Conclusion

Results