Endocrine Abstracts

The endogenous growth hormone secretagogue (GHS), ghrelin, is an important regulator of energy homeostasis. Peripheral and central administration of ghrelin increase food intake, body weight and fat mass, effects which are mediated by the growth hormone secretagogue receptor type 1a (GHS-R 1a). Although the central actions of ghrelin on adiposity have been extensively studied, the direct peripheral effects of ghrelin on adipose tissue remain poorly understood. This study aimed 1) to examine GHS-R 1a expression in adipose tissue depots 2) to investigate the effect of ghrelin on basal and insulin-stimulated glucose uptake in adipocytes from GHS-R 1a positive and negative fat pads and 3) to determine the action of des-acyl ghrelin, which does not bind GHS-R 1a, on basal and insulin stimulated glucose uptake.

RT-PCR demonstrated differential expression of GHS-R 1a mRNA in fat pads. Expression was detected in mRNA extracted from epididymal, omental and pericardial adipose tissue but absent in mRNA from subcutaneous and perirenal adipose tissue. The effect of ghrelin (10 to 1000nM) on basal and insulin-stimulated glucose uptake was examined in adipocytes from dispersed epididymal and perirenal fat pads. Ghrelin did not alter basal glucose uptake but dose-dependently increased insulin-stimulated glucose uptake in adipocytes harvested from epididymal fat pads and expressing GHS-R1a. In contrast, ghrelin had no effect on glucose uptake in adipocytes from perirenal fat pads lacking GHS-R1a. To further investigate the role of GHS-R1a in ghrelin's actions on glucose uptake, the effects of des-acyl ghrelin were examined. Des-acyl ghrelin did not alter basal or insulin-stimulated glucose uptake in dispersed adipocytes.

These data suggest ghrelin has direct actions on adipocyte function, acting directly at the level of the adipocyte to potentiate insulin-stimulated glucose uptake. Moreover, in common with the orexigenic actions of ghrelin, it is likely that these effects are mediated by GHS-R1a.