Effect of Peripheral Kisspeptin Administration on Adiponectin, Leptin, and Resistin Secretion Under Fed and Fasting Conditions in the Adult Male Rhesus Monkey (Macaca mulatta)

Abstract

In the last few years, kisspeptin-KISS1R signaling has appeared as a major regulator of the reproductive function in several vertebrate species. However, KISS1(encoding kisspeptin) and its putative receptor, KISS1R, are expressed in several other tissues. Adipose tissue, which secretes many peptides with diverse functions in normal physiology, expresses KISS1, which is modulated by gonadal steroids as well as by body nutritional status. Similarly, KISS1Rexpression is also found in adipose tissue, but the local role of kisspeptin in adipocyte function is currently unknown. Therefore, in the present study the effects of exogenous human kisspeptin-10 (KP10) were studied on three important adipokines, namely, adiponectin, leptin, and resistin in a set of four chair-restraint habituated intact adult male rhesus monkeys under; 1) normal fed conditions, 2) 24-h fasting conditions, and 3) 48-h fasting conditions. Plasma resistin and leptin levels decreased (p<0.01), whereas adiponectin levels increased (p<0.05) in fasted monkeys. Kisspeptin administration significantly increased (p<0.05) mean plasma adiponectin levels under fed and 24-h fasting conditions as compared to pretreatment or vehicle-treatment levels. A stimulatory effect was also observed on the 48-h fasting stimulated plasma adiponectin levels, but it lacked statistical significance. In contrast, no effect of kisspeptin was observed on mean plasma leptin and resistin levels. Thus, the present study demonstrated a stimulatory effect of peripheral kisspeptin administration on the plasma adiponectin levels under fed and 24-h fasting conditions in the adult male rhesus monkey. These findings, therefore, assign a novel role to kisspeptin, a regulator of adipocyte function in higher primate.

Peripheral administration of kisspeptin antagonist does not alter basal plasma testosterone but decreases plasma adiponectin levels in adult male rhesus macaques

“…Our previous study indicated that the kisspeptin significantly increased plasma adiponectin levels in the adult male rhesus monkey (Wahab et al, 2010). This was a novel finding and suggested that kisspeptin acted peripherally on adipose tissues and stimulated adiponectin release.…”

“…Blood samples were collected at 15-min intervals for 60 min before P234/ vehicle administration and until 210 min after the KP-10 administration. As mentioned above, the doses of P234 and KP-10 were calculated based on previous work in adult female (Roseweir et al, 2009) and adult male (Wahab et al, 2010) rhesus monkeys, respectively. 2.5.…”

“…The effect of the kisspeptin receptor blockade on plasma adiponectin levels was used as a positive control for the peripheral effects of kisspeptin, as kisspeptin had been found previously to act peripherally to increase adiponectin secretion (Wahab et al, 2010).…”

“…The pivotal role of kisspeptin-GPR54 signaling in reproductive function has been demonstrated in a number of pharmacological (Shahab et al, 2005;Wahab et al, 2010) and gene expression (Brown et al, 2008) studies. However, the physiological significance of this signaling has not been well characterized.…”

“…In recent years, the discovery of a kisspeptin antagonist, peptide 234 (P234), and its use in animal investigations has helped to shed light on the role of endogenous kisspeptin signaling in regulating the reproductive axis. These studies have provided detailed evidence for a physiological role of kisspeptin signaling in regulating GnRH secretion in mammals (Shahab et al, 2005;Brown et al, 2008;Roseweir et al, 2009;Wahab et al, 2010;Pineda et al, 2010;Guerriero et al, 2012). However, few studies have been directed at examining testosterone release in primates in response to peripheral kisspeptin, and the few studies that have used P234 have predominantly administered the antagonist centrally within the nervous system.…”