Abstract
Jerboas are wild rodents exhibiting exceptional adaptation to their desert environment. Under harsh autumn conditions, they shut down reproduction, increase body weight and hibernate, while during spring they become sexually active even under negative energy-balance. We recently reported that these rhythms are associated with synchronized changes in genes expressing reproductive (Kiss1, Rfrp) and metabolic (Npy and Pomc) peptides, raising the hypothesis of coordinated seasonal regulation of both functions. Here we analyzed whether kisspeptin and RFRP-3 regulate food-intake in parallel to their established reproductive functions. Intracerebroventricular administration of kisspeptin inhibited food intake by 1.5-fold in fasted, but not ad-libitum fed, female jerboas captured in spring, an effect associated with an increase in Pomc and decrease in Rfrp mRNA levels. By contrast, intracerebroventricular injection of RFRP-3 induced a 4-fold increase in food-intake in ad-libitum female jerboas, together with a decrease in Pomc and increase in Npy mRNA levels. This orexigenic effect of RFRP-3 was observed in both spring and autumn, whereas kisspeptin’s anorexigenic effect was only observed in spring. Altogether, this study reports opposite metabolic effects of kisspeptin and RFRP-3 in the female jerboa and strengthens our hypothesis of a coordinated, season-dependent, regulation of reproductive activity and food intake through interactions of these hypothalamic peptides.
Highlights
Jerboas are wild rodents exhibiting exceptional adaptation to their desert environment
Major progress has been made recently in the understanding of central mechanisms governing reproductive activity with the finding that two hypothalamic peptides, kisspeptin (Kp) and RF amide-related peptide 3 (RFRP-3, known as gonadotropin inhibitory hormone) regulate GnRH neuronal activity and gonadotropin secretion[1,2]. We examine whether these two reproductive neuropeptides alter metabolism by investigating their effect on food intake and the metabolic neuropeptides proopiomelanocortin (POMC) and neuropeptide Y (NPY) in a wild hibernating seasonal rodent captured from its natural biotope, the jerboa (Jaculus orientalis)
Kp10 strongly decreased food intake in fasted female jerboas captured in spring (Fig. 1A) with a significant reduction of food intake as early as 1 hour post-injection (−50%, P < 0.05 compared with vehicle treated animals)
Summary
Jerboas are wild rodents exhibiting exceptional adaptation to their desert environment. Intracerebroventricular administration of kisspeptin inhibited food intake by 1.5-fold in fasted, but not ad-libitum fed, female jerboas captured in spring, an effect associated with an increase in Pomc and decrease in Rfrp mRNA levels. This study reports opposite metabolic effects of kisspeptin and RFRP-3 in the female jerboa and strengthens our hypothesis of a coordinated, season-dependent, regulation of reproductive activity and food intake through interactions of these hypothalamic peptides. RFRP-3 increases food intake in rodents, sheep and non-human primates[21,22,23,24] while Kp displays an anorexigenic effect in overnight fasted mice[25] In line with these feeding behaviors, other studies indicate that both peptides may regulate POMC or NPY arcuate neurons. RFRP-3 projects to NPY and POMC neurons in the ewe[30], attenuates the action of Kp on POMC neurons in mice[29] and increases NPY gene expression in the rat[23]
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