Changes in Expression of the Genes for the Leptin Signaling in Hypothalamic-Pituitary Selected Areas and Endocrine Responses to Long-Term Manipulation in Body Weight and Resistin in Ewes.

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

doi:10.3390/ijms21124238

Abstract

Both long-term undernutrition and overnutrition disturb metabolic balance, which is mediated partially by the action of two adipokines, leptin and resistin (RSTN). In this study, we manipulated the diet of ewes to produce either a thin (lean) or fat (fat) body condition and investigated how RSTN affects endocrine and metabolic status under different leptin concentrations. Twenty ewes were distributed into four groups (n = 5): the lean and fat groups were administered with saline (Lean and Fat), while the Lean-R (Lean-Resistin treated) and Fat-R (Fat-Resistin treated) groups received recombinant bovine resistin. Plasma was assayed for LH, FSH, PRL, RSTN, leptin, GH, glucose, insulin, total cholesterol, nonesterified fatty acid (NEFA), high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Expression levels of a suppressor of cytokine signaling (SOCS-3) and the long form of the leptin receptor (LRb) were determined in selected brain regions, such as the anterior pituitary, hypothalamic arcuate nucleus, preoptic area and ventro- and dorsomedial nuclei. The results indicate long-term alterations in body weight affect RSTN-mediated effects on metabolic and reproductive hormones concentrations and the expression of leptin signaling components: LRb and SOCS-3. This may be an adaptive mechanism to long-term changes in adiposity during the state of long-day leptin resistance.

Highlights

Leptin, an adipocyte hormone that is secreted in proportion to body fat levels, inhibits food intake to provide feedback control of fat mass, facilitating maintenance of a constant body weight (BW) [1]
Numerous studies suggest that adipocyte-derived RSTN and leptin directly regulate both feeding and peripheral metabolism through, so far for RSTN undefined hypothalamic-mediated mechanisms [24,25]
Arcuate neurons are characterized by a large number of receptors for peripheral peptides, such as leptin (LRb), insulin (IR) and RSTN (TLR4) [26]

Summary

Introduction

An adipocyte hormone that is secreted in proportion to body fat levels, inhibits food intake to provide feedback control of fat mass, facilitating maintenance of a constant body weight (BW) [1]. The first significant evidence for that hypothesis was provided by Asterholm’s group, who showed that chronically elevated RSTN concentrations lead to leptin resistance and reduced the expression of leptin signaling components, namely, suppressor of cytokine signaling-3 (SOCS-3) in the hypothalamic nuclei [6] This supports our earlier suggestions that an increase in the expression of SOCS-3 in the ARC may be an executive player in the development of leptin resistance in sheep [7,8,9]. Another confirmation supporting our hypothesis was provided by a study from Friedman’s group demonstrating that leptin-deficient animals in which BWt was normalized by chronic low-level leptin infusion remained responsive to leptin, even when obesity was induced by a high-fat diet (HFD) [10]. It has been suggested that RSTN is involved in the regulation of seasonal reproduction in sheep [11]

Methods

Results

Conclusion