Kisspeptin and RFRP3 modulate body mass in Phodopus sungorus via two different neuroendocrine pathways

Many animals exhibit remarkable metabolic and reproductive adaptations to seasonal changes in their environment. When day length shortens, Djungarian hamsters (Phodopus sungorus) reduce their body weight and inhibit their reproductive activity, while the opposite occurs in springtime. These physiological adaptations are thought to depend on photoperiodic changes in hypothalamic genes encoding the peptides kisspeptin and RFRP3 for the control of reproduction, and pro-opiomelanocortin and somatostatin for metabolic regulation. The objective of this study was to investigate the effect of kisspeptin and RFRP3 on long-term body weight regulation in order to establish whether metabolic and reproductive hypothalamic networks may interact during adaptation to seasonal physiology. We found that chronic central administration of both kisspeptin or RFRP3 in short photoperiod-adapted male Djungarian hamsters increased body weight although through different pathways. The effect of kisspeptin was dependent on testicular activity, as castration prevented the body weight increase, and was associated with an increase in pro-opiomelanocortin and neuropeptide Y expression. On the other hand, the orexigenic effect of RFRP3 was associated with an increase in circulating insulin and leptin levels, but had no effect on any of the hypothalamic metabolic genes investigated, and did not change circulating levels of sex steroids. Notably, neither kisspeptin nor RFRP3 altered female hamster’s metabolic parameters. Thus, using a rodent model exhibiting seasonal changes in reproduction and metabolism, this study demonstrates that in addition to its role in the central control of reproduction kisspeptin also participates in body weight control in a sex dependent manner through an anabolic action of testosterone. Conversely, RFRP3 affects body weight control in males mostly by acting on adiposity with no overt effect on the reproductive system in both sexes. This article is protected by copyright. All rights reserved.