Hypothalamic-Pituitary and Adipose Tissue Responses to the Effect of Resistin in Sheep: The Integration of Leptin and Resistin Signaling Involving a Suppressor of Cytokine Signaling 3 and the Long Form of the Leptin Receptor.

Dorota Anna Zieba,Katarzyna Kirsz,Malgorzata Szczesna,Weronika Biernat,Tomasz Misztal

doi:10.3390/nu11092180

Abstract

We hypothesized that resistin is engaged in the development of leptin central insensitivity/resistance in sheep, which is a unique animal model to explore reversible leptin resistance. Thirty Polish Longwool ewes, which were ovariectomized with estrogen replacement, were used. Treatments consisted of the intravenous injection of control (saline) or recombinant bovine resistin (rbresistin): control (Control; n = 10), a low dose of rbresistin (R1; 1.0 μg/kg body weight (BW); n = 10), and a high dose of rbresistin (R2; 10.0 μg/kg BW; n = 10). The studies were performed during short-day (SD) and long-day (LD) photoperiods. Leptin and resistin concentrations were determined. Expression levels of a suppressor of cytokine signaling (SOCS)-3 and the long form of the leptin receptor (LeptRb) were determined in selected brain regions, including in the anterior pituitary (AP), hypothalamic arcuate nucleus (ARC), preoptic area (POA), and ventro- and dorsomedial nuclei (VMH/DMH). The results indicate that resistin induced a consistent decrease in LeptRb (except in POA) and an increase in SOCS-3 expression during the LD photoperiod in all selected brain regions. In conclusion, the results demonstrate that the action of resistin appears to be strongly associated with photoperiod-driven changes in the leptin signaling pathway, which may underlie the phenomenon of central leptin resistance.

Highlights

Sheep, which have strong seasonal breeding features, are characterized by circannual rhythms for the secretion of many hormones, food intake and body weight (BW), which makes them an elegant animal example for determining neuroendocrine adaptations of animals to challenging environmental conditions [1]
This paper addresses the important question of whether resistin is able to affect leptin secretion from adipose tissue or leptin signaling at the level of the hypothalamus and adenohypophysis and as a result, contribute to the progression of the leptin resistance phenomenon in sheep
9.5 ± 0.2 ng/mL, and the 10.0 μg/kg BW dose of rbresistin elevated the concentration of resistin to

Summary

Introduction

Sheep, which have strong seasonal breeding features, are characterized by circannual rhythms for the secretion of many hormones, food intake and body weight (BW), which makes them an elegant animal example for determining neuroendocrine adaptations of animals to challenging environmental conditions [1]. One such adaptation is the development of leptin resistance/insensitivity. Since 2004, studies by our laboratory have focused mainly on central leptin resistance caused by the elevated expression of SOCS-3 during the long-day (LD) season [6,7]. If significant changes in seasonal leptin insensitivity occur at the hypothalamic–pituitary level in sheep [5,7], questions arise regarding how this effect is mediated

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Discussion

Conclusion