Seasonal and Nutritional Fluctuations in the mRNA Levels of the Short Form of the Leptin Receptor (LRa) in the Hypothalamus and Anterior Pituitary in Resistin-Treated Sheep

Abstract

The short form of the leptin receptor (LRa) plays a key role in the transport of leptin to the central nervous system (CNS). Here, the resistin (RSTN)-mediated expression of LRa in the preoptic area (POA), ventromedial and dorsomedial nuclei (VMH/DMH),arcuate nucleus (ARC) and the anterior pituitary gland (AP)was analyzed considering the photoperiodic (experiment 1) and nutritional status (experiment 2) of ewes. In experiment 1, 30 sheep were fed normally and received one injection of saline or two doses of RSTN one hour prior to euthanasia. RSTN increased LRa expression mainly in the ARC and AP during long days (LD) and only in the AP during short days (SD). In experiment 2, an altered diet for 5 months created lean or fat sheep. Twenty sheep were divided into four groups: the lean and fat groups were given saline, while the lean-R and fat-R groups received RSTN one hour prior to euthanasia. Changes in adiposity influenced the effect of RSTN on LRa mRNA transcript levels in the POA, ARC and AP and without detection of LRa in the VMH/DMH. Overall, both photoperiodic and nutritional signals influence the effects of RSTN on leptin transport to the CNS and are involved in the adaptive/pathological phenomenon of leptin resistance in sheep.

Seasonal and nutritional changes in the short form of the leptin receptor expression and VEGF system in the choroid plexus, arcuate nucleus, and anterior pituitary in MTS-leptin and resistin-treated sheep

“…The results showed that the nutritional status of sheep affected the concentration of endogenous leptin after treatment with MTS-leptin and/or recombinant oleptin, and the differences were dependent on photoperiod, with a weaker effect of MTS-leptin. The concentration of leptin was higher in fasted ewes during the LD season in all experimental groups, as we observed in our previous experiments on cattle and sheep ( Zieba et al, 2003 , 2008 ; Biernat et al, 2021 ). In prepubertal heifers, leptin gene expression and circulating leptin were markedly reduced in fasted (60 h) compared to fed females ( Amstalden et al, 2000 ), and the leptin concentration was 2- or 3-fold lower in SD vs. LD sheep ( Biernat et al, 2021 ).…”

“…The concentration of leptin was higher in fasted ewes during the LD season in all experimental groups, as we observed in our previous experiments on cattle and sheep ( Zieba et al, 2003 , 2008 ; Biernat et al, 2021 ). In prepubertal heifers, leptin gene expression and circulating leptin were markedly reduced in fasted (60 h) compared to fed females ( Amstalden et al, 2000 ), and the leptin concentration was 2- or 3-fold lower in SD vs. LD sheep ( Biernat et al, 2021 ).…”

“…The blood-brain barrier (BBB) is a key player in adipokine signaling from the periphery to the central nervous system (CNS). The results of our previous study demonstrate that photoperiodic and nutritional signals influence the effects of resistin on leptin transport to the CNS via the LeptRa isoform and that leptin action in the hypothalamus via the LeptRb isoform and resistin is involved in the adaptive/pathological phenomenon of leptin resistance in sheep, affecting the expression of SOCS3 (Król et al, 2007;Zieba et al, 2019;Biernat et al, 2021). To act centrally, leptin from circulating blood must first enter the brain, thereby passing through the bloodcerebrospinal fluid barrier (BCSFB) at the choroid plexus (ChP) and/ or the BBB at the cerebral endothelium in the CNS.…”

Effects of Leptin, Growth Hormone and Photoperiod on Pituitary SOCS-3 Expression in Sheep

“…The intracellular signaling pathways of leptin and GH can be positively and negatively regulated. One of the major negative regulators of these pathways is the suppressor of cytokine signaling-3 (SOCS-3) protein, which can suppress the actions of both GH [10][11][12] and leptin [13]. Transcription of the SOCS-3 gene is not constitutive in a majority of tissues (except in the brain), and thus specific factors are needed to induce its transcription.…”

“…Transcription of the SOCS-3 gene is not constitutive in a majority of tissues (except in the brain), and thus specific factors are needed to induce its transcription. SOCS-3 and many factors that induce its expression are localized in the arcuate nucleus (ARC), paraventricular nucleus (PVN), ventromedial and dorsomedial nuclei, suprachiasmatic nucleus [11,14], and the pituitary gland, suggesting that SOCS-3 may play a pivotal role in modulating neuroendocrine interactions among hormones, such as leptin, prolactin (PRL), and resistin [12]. Data suggest that SOCS-3 plays a significant role in the pituitary gland.…”