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

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.

Keywords: LRb; RSTN; SOCS-3; leptin; nutrition; sheep.

Figure 1

Temporal changes in body weight in lean and fat animals; which were maintained until July (time of experiment).

Figure 2

Leptin receptor mRNA expression. The mean mRNA expression (±SEM) of the long form of the leptin receptor (LRb) in the ovine anterior pituitary gland (AP), arcuate nucleus (ARC), preoptic area (POA) and ventro- and dorsomedial nuclei (VMH/DMH) collected during a long-day (LD) photoperiod in nontreated (Lean and Fat) animals and animals treated with recombinant bovine resistin (Lean-R [Lean-Resistin treated] and Fat-R [Fat-Resistin treated]. The expression of LRb mRNA is reported in arbitrary units (RQ) relative to cyclophilin mRNA expression and expressed relative to the calibrator sample. Differences relative to the control or between the other groups are indicated with ** p < 0.05, *** p < 0.001. Samples in which the expression of the target gene was undetectable are designated with ND.

Figure 3

Expression of SOCS-3. The mean expression (±SEM) of a suppressor of cytokine signaling-3 (SOCS-3) mRNA in the ovine anterior pituitary (AP), arcuate nucleus (ARC), preoptic area (POA) and ventro- and dorsomedial nuclei (VMH/DMH) collected during long-day (LD) photoperiod in nontreated (Lean and Fat) animals and animals treated with recombinant bovine resistin (Lean-R [Lean-Resistin treated] and Fat-R [Fat-Resistin treated]. The expression of SOCS-3 mRNA is reported in arbitrary units (RQ) relative to cyclophilin mRNA and expressed relative to the calibrator sample. Differences relative to the control or between the other groups are indicated with ** p < 0.05 or *** p < 0.001.