Obesity and leptin resistance: The role of growth hormone

Abstract

Decreased growth hormone (GH) function in obese patients might contribute to associated metabolic abnormalities. This study aimed to investigate the effect of leptin, GH and periods of leptin sensitivity or/and insensitivity on the expression of the SOCS-3 gene in the ovine pituitary and to examine the influence of centrally administered leptin on GH release in sheep. Our first experiment investigated the periods of leptin resistance and leptin sensitivity, which are known as the long day (LD) and the short day (SD) periods, respectively, using ewes that were surgically fitted with third ventricular cannulae. The ewes were assigned randomly to one of three treatments and were centrally infused at 0, 1 and 2 h, beginning at sunset. The treatments consisted of central infusions of either Ringer-Locke buffer or leptin (0.5 or 1.0 μg/kg body weight (BW), respectively). Our next experiment examined the pituitaries isolated from ewes decapitated in either May or November. The explants were treated with control or GH (100 or 300 ng/ml) or leptin (50 or 100 ng/ml) — containing media and incubated for one of four different time intervals. The in vivo experiments demonstrated variable effects of leptin on GH release depending on the period of leptin sensitivity/ insensitivity. The in vitro experiments demonstrated that leptin significantly influenced the expression of the SOCS-3 gene during that SD compared to that during the LD. During the SD, we observed that significantly low or high doses of GH affected the expression of SOCS-3. These results indicated a strong correlation between leptin or GH and SOCS-3, which might explain leptin resistance and the associated perturbations in GH signaling.