The Role of Ghrelin and Growth Hormone Secretagogues Receptor on Rat Adipogenesis

Abstract

Recent research progress indicates a close link between ghrelin, a natural ligand of GH secretagogues receptor (GHS-R), and both the metabolic balance and body composition. To clarify the involvement of ghrelin and GHS-R in the process of adipogenesis, we measured the expression of GHS-R and peroxisome proliferator-activated receptor gamma 2 (PPAR-gamma 2) mRNA in rat adipocytes using semiquantitative RT-PCR methods. The levels of GHS-R mRNA increased by up to 4-fold in adipose tissue from epididymal and parametrial regions as the rat aged from 4-20 wk and were significantly elevated during the differentiation of preadipocytes in vitro. Ghrelin (10(-8) M for 10 d) stimulated the activity of glycerol-3-phosphate dehydrogenase and the differentiation of rat preadipocytes in vitro. Ghrelin treatment also significantly increased the levels of PPAR-gamma 2 mRNA in primary cultured rat differentiated adipocytes. In addition, isoproterenol (10(-8) M, 40 min)-stimulated lipolysis was significantly reduced by simultaneous ghrelin treatment in a dose-dependent manner in vitro. In conclusion, the expression of GHS-R in rat adipocytes increases with the age and during adipogenesis. Ghrelin in vitro stimulates the differentiation of preadipocytes and antagonizes lipolysis. Ghrelin may therefore play an important role in the process of adipogenesis in rats.

Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes

“…51 In line with this, our findings show that acylated and desacyl ghrelin treatment reduced adipophilin levels, the protein surrounding lipid droplets of preadipocytes, and increased the expression of perilipin, the protein coating lipid droplets in mature adipocytes. On the basis of our results, as well as on the studies carried out in experimental models, [19][20][21] it can be concluded that acylated and desacyl ghrelin directly increase adiposity in human visceral adipocytes, independently of its orexigenic action.…”

“…In this regard, GHS-R is reportedly expressed in rat adipocytes and in other cell types of the stromovascular fraction, such as rat preadipocytes, human endothelial cells, monocyte-macrophages or T cells. 19,46,47 Moreover, a decrease in the GHS-R 1a protein expression in the visceral adipose tissue of obese individuals Lipogenic effect of ghrelin in humans A Rodríguez et al was observed. A plausible explanation for this finding may be that acylated ghrelin, which is increased in obese subjects, downregulates its own receptor in visceral adipocytes, as it does in several cell types, such as chicken and porcine pituitary somatotropes 48,49 or rat hypothalamic neurones.…”

“…6,[9][10][11] Earlier studies suggest that the adipose tissue also constitutes an important target for the adipogenic actions of ghrelin in rodents. 19,21 This study has explored whether acylated and desacyl ghrelin directly act on visceral adipose tissue for regulating adipocyte metabolism in humans. The main findings are that: (1) circulating acylated ghrelin concentrations are increased in obese patients; (2) GHS-R 1a is expressed in omental adipose tissue; (3) the expression of this ghrelin receptor is decreased in obesity and obesityassociated T2D; and (4) acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes.…”

“…6,18 Moreover, it has been suggested that acylated ghrelin directly acts on adipocytes for stimulating adipogenesis in rodents. [19][20][21] Nonetheless, these data are not univocal, as other authors have reported that overexpression of ghrelin inhibits adipocyte differentiation in 3T3-L1 adipocytes, and that the genetic deletion of ghrelin or its receptor in mice induces thymic adipogenesis. 22,23 These contradictory observations raise some questions regarding the involvement of ghrelin in the control of adipocyte metabolism.…”

The Relationship of Ghrelin and Leptin with the Biochemical Markers for Adult Growth Hormone Deficiency

“…Ghrelin은 순환하는 식욕증진 호르몬으로 알려져 있고 [7], ghrelin의 농도는 식사 전에 증가하고 식사 후에 감소하는 것으로 보아 음식 섭취를 유도하는 역할을 하는 것으로 추정된다 [6,8]. Ghrelin은 양(positive)의 에너 지 균형을 조장하고 설치류에서 지방 이용률을 감소시켜 지 방과다를 유도한다 [9]. Ghrelin 농도는 비만한 사람에서 감 소되어있고 식이요법에 의한 체중 감소 후에는 증가되는 것 으로 알려져 있다 [6,8,10,11].…”