Kisspeptin and Glucose Homeostasis

Abstract

Kisspeptin has well-established critical roles in the control of reproduction and fertility. Recently, evidence has emerged that suggests kisspeptin may have additional roles in the regulation of glucose homeostasis. Conflicting reports on the effects of kisspeptin on insulin secretion in animal models have been published, which cannot be fully accounted for by the different kisspeptin isoforms and range of kisspeptin doses used in these studies. Human studies have demonstrated associations between circulating kisspeptin levels and measures of insulin secretion and insulin resistance; and the only published interventional study has confirmed kisspeptin enhances glucose-stimulated insulin secretion in humans. Further studies are required to elucidate the mechanisms underlying the effects of kisspeptin on the pancreatic β-cell and to determine the therapeutic potential of kisspeptin receptor agonist in the treatment of disorders of glucose homeostasis.

Sexually dimorphic pubertal development and adipose tissue kisspeptin dysregulation in the obese and preeclamptic-like BPH/5 mouse model offspring

“…Kisspeptins are considered the “gatekeepers” of the hypothalamic-pituitary-gonadal axis, since hypothalamic kisspeptin signaling is critical for pubertal development and reproduction in males and females ( de Roux et al, 2003 ; Funes et al, 2003 ; Seminara et al, 2003 ; Lapatto et al, 2007 ; Tassigny et al, 2007 ). Besides their role in the central nervous system, kisspeptins seem to have important roles in peripheral metabolic tissues, including sex-specific regulation of adiposity ( Hussain et al, 2015 ; Dudek et al, 2018 ; Wang et al, 2018 ; Izzi-Engbeaya et al, 2019 ; Hudson and Kauffman, 2022 ). Altered adipose tissue Kiss1 expression has been previously associated with obesity in rats and humans ( Brown et al, 2008 ; Cockwell et al, 2013 ).…”

“…Studies in gonadectomized rats suggest that both sex steroid hormones and nutrition modulate adipose tissue Kiss1 ( Brown et al, 2008 ) . Therefore, similar to the central nervous system, we speculate that kisspeptins are also the “missing link” in the crosstalk between reproduction and metabolism in peripheral tissues ( Hussain et al, 2015 ; Dudek et al, 2018 ; Harter et al, 2018 ; Izzi-Engbeaya et al, 2019 ; Hudson and Kauffman, 2022 ; Musa et al, 2022 ).…”

“…Kisspeptins are a family of small peptides encoded by the Kiss1 gene with sex-specific roles in reproduction and metabolism ( Hussain et al, 2015 ; Dudek et al, 2018 ; Harter et al, 2018 ). Besides the central role of kisspeptins in the activation of the hypothalamic-pituitary-gonadal axis, this family of peptides appear to be important peripheral regulators of metabolism, energy expenditure, thermoregulation and adipogenesis ( Hussain et al, 2015 ; Dudek et al, 2018 ; Harter et al, 2018 ; Izzi-Engbeaya et al, 2019 ; Hudson and Kauffman, 2022 ; Musa et al, 2022 ). In vitro studies suggest that kisspeptins may induce lipolysis and impair adipocyte glucose uptake in rodents and humans ( Hussain et al, 2015 ; Pruszynska-Oszmalek et al, 2017 ; Dudek et al, 2018 ; Hudson and Kauffman, 2022 ).…”

LKB1 alleviates high glucose‑ and high fat‑induced inflammation and the expression of GnRH and sexual precocity‑related genes, in mouse hypothalamic cells by activating the AMPK/FOXO1 signaling pathway

“…Furthermore, ERs exert strong effects on the maintenance of female secondary sexual characteristics and reproductive cycles and affect fertility ( 22 ). Estrogen and its receptors adjust the synthesis and release of GnRH by acting on GnRH neurons in the hypothalamus, thereby regulating the entire reproductive system ( 23 ). ERβ, CD36 and GPR54 are important ER- and sexual precocity-related genes, which have been shown to be expressed in GT1-7 cells ( 7 ).…”

Effects of High-Glucose and High-Fat Condition on Estrogen Receptor- and Sexual Precocity-Related Genes in GT1-7 Cells

“…Estrogen receptors play a key role in the maintenance of secondary sexual characteristics and reproductive cycles in females and affects fertility [13]. Estrogen and its receptors regulate GnRH synthesis and release it by directly or indirectly acting on GnRH neurons in the hypothalamus, and then regulate the whole reproductive system [14,15]. GT1-7 cells can express the morphology of primitive GnRH neurons, gene GnRH, KiSS-1, and GPR54, and can pulse-release GnRH.…”