Impact of food restriction on the medio‐basal hypothalamus of intact ewes as revealed by a large‐scale transcriptomics study

Abstract

In mammals, the medio-basal hypothalamus (MBH) integrates photoperiodic and food-related cues to ensure timely phasing of physiological functions, including seasonal reproduction. The current human epidemics of obesity and associated reproductive disorders exemplifies the tight link between metabolism and reproduction.Yet, how food-related cues impact breeding at the level of the MBH remains unclear.In this respect, the sheep, which is a large diurnal mammal with a marked dual photoperiodic/metabolic control of seasonal breeding, is a relevant model. Here, we present a large-scale study in ewes (n = 120), which investigated the impact of food restriction (FRes) on the MBH transcriptome using unbiased RNAseq, followed by RT-qPCR. Few genes (~100) were impacted by FRes and the transcriptional impact was very modest (<2-fold increase or < 50% decrease for most genes). As anticipated, FRes increased expression of Npy/AgRP/LepR and decreased expression of Pomc/Cartpt, while Kiss1 expression was not impacted. Of particular interest, Eya3, Nmu and Dio2, genes involved in photoperiodic decoding within the MBH, were also affected by FRes. Finally, we also identified a handful of genes not known to be regulated by food-related cues (e.g., RNase6, HspA6, Arrdc2). In conclusion, our transcriptomics study provides insights into the impact of metabolism on the MBH in sheep, which may be relevant to human, and identifies possible molecular links between metabolism and (seasonal) reproduction.

Interactions between β‐endorphin and kisspeptin neurons of the ewe arcuate nucleus are modulated by photoperiod

“…Of note, KP synthesis is modulated by photoperiod as short-days (SD) promote an increase of KP levels in the ovine ARC (20)(21)(22) and KP terminals on GnRH neurons are more numerous during the breeding season (23). KP neurons are also sensitive to the metabolic status of animals as KP levels in lean ovariectomized ewes are decreased compared to well-fed ewes (24,25). KP neurons express leptin receptors Ob-R and have reciprocal connections with neuropeptide Y and POMC-expressing neurons within the ARC (24), which suggests a role as metabolic sensors for KP neurons of the ARC.…”

“…23 KP neurons are also sensitive to the metabolic status of animals as KP levels in lean ovariectomized (OVX) ewes are decreased compared to well-fed ewes. 24,25 KP neurons express leptin receptors Ob-R and have reciprocal connections with neuropeptide Y and POMC-expressing neurons within the ARC, 24 which suggests a role as metabolic sensors for KP neurons of the ARC. In addition to this metabolic modulation, the activity of KP neurons from the ARC is regulated by neurokinin B, and dynorphin, two peptides cosynthetized within KP neurons; hence their KNDy nickname.…”