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.

Weronika Biernat,Dorota Anna Zieba,Katarzyna Kirsz,Malgorzata Szczęsna

doi:10.3390/ani11082451

Weronika Biernat, Dorota Anna Zieba + Show 2 more

Open Access

https://doi.org/10.3390/ani11082451

Copy DOI

Abstract

Simple SummaryResearch since the discovery of leptin has mainly focused on the long form of the leptin receptor. Currently, experiments on the short form of the leptin receptor have confirmed that not only is short form of leptin receptor present in the hypothalamus, but also expanded knowledge with information documenting the specific expression of that form of leptin receptor in selected areas of the hypothalamus and in the pituitary gland. In addition, we have shown that short form of leptin receptor expression levels are affected by day length, adiposity and resistin in sheep.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.

Highlights

Domestication has led to an almost complete loss of seasonality in cattle, but it is retained in most breeds of sheep or goats [1]
Taking into account the research model—seasonally breeding sheep—we investigated the role of photoperiod, nutritional status and RSTN, which enters the brain via the blood–brain barrier (BBB) due to its low weight of 12.5 kD and is involved in the interaction between leptin resistance and increased expression of suppressor cytokine signaling 3 (SOCS3) [5,18]
LRa transcripts were detected at varying levels in the examined hypothalamic tissues, namely, the preoptic area (POA) and arcuate nucleus (ARC); no detection was noted in the VMH/DMH during either the long day (LD) or short days (SD) seasons (Figure 1A,B)

Summary

Introduction

Domestication has led to an almost complete loss of seasonality in cattle, but it is retained in most breeds of sheep or goats [1]. Our most recent data show that RSTN is involved in this photoperiod and nutrition-dependent central leptin insensitivity in sheep which in that species occurs only during long day (LD) season [5,6]. Six isoforms of LRs have been described far (LRa-f), the most important of which is the long isoform—LRb—because only this form is able to activate the main pathway of cell leptin signaling—JAK2-STAT3 [7]. An inhibitor of this leptin signaling pathway in the cell is suppressor cytokine signaling 3 (SOCS3), which inhibits leptin receptor phosphorylation [8]. Despite the high concentration of this anorectic hormone in the circulation, it has no effect on food intake

Objectives

Methods

Results

Discussion

Conclusion