Inhibition of growth hormone secretagogue receptor antagonist, [D‐Lys‐3]‐GHRP‐6, in adipogenesis of ovine and rat adipocytes

Abstract

Ghrelin and growth hormone secretagogues receptor (GHS-R or ghrelin receptor) have been reported as being one of the factors of adipogenesis in adipocytes. To investigate the involvement of ghrelin and GHS-R in adipocytes, the effect of the GHS-R antagonist, [D-Lys-3]-GHRP-6 (His-D-Trp-D-Lys-Trp-D-Phe-Lys-NH 2 ), on the process of adipogenesis in ovine and rat adipocytes was evaluated. [D-Lys-3]-GHRP-6 (10 -7 mol/L) significantly inhibited adipogenic differentiation of ovine and rat preadipocytes prepared from adipose tissues. The level of peroxisome proliferator activated receptor (PPAR)-g 2 mRNA, an adipogenic marker, was decreased during the differentiation of adipocytes treated with [D-Lys-3]-GHRP-6 for 10 days. Ghrelin stimulated adipogenesis, also causing an increment of glycerol-3-phosphate dehydrogenase and upregulation of PPAR-g 2. Furthermore, the antilipolytic effect of ghrelin was attenuated by treatment with [D-Lys-3]-GHRP-6 in both types of isolated adipocytes. Overall, the results of the present study highlight that GHS-R in adipogenesis can be blocked by treatment with [D-Lys-3]-GHRP-6.

Inhibition of Ghrelin Activity by Receptor Antagonist [d-Lys-3] GHRP-6 Attenuates Alcohol-Induced Hepatic Steatosis by Regulating Hepatic Lipid Metabolism

“…The diet contains 11% carbohydrates, 18% protein, 35% fat and 36% ethanol of total calories with ethanol being replaced isocalorically with maltodextrin in the control diet [22]. After 6 weeks of feeding, half of the rats in the control group and ethanol-fed group received intraperitoneal injection of DLys, a peptide GHS-R1a antagonist at a dose of 9 mg/kg BW for 5 days while the other half received saline injection [18,19,20]. During the treatment period (5 days), all rats were pair-fed to the ethanol rats being administered the antagonist.…”

“…We hypothesized that treatment with a selective ghrelin receptor antagonist will prevent the alcohol-induced effect on pancreas, adipose tissue, and the liver. [D-Lys3]-GHRP-6 (DLys) is one such selective GHS-R1a antagonist that is widely used in in vivo and in vitro [17,18,19,20]. In this study, we examined its effect on alcohol-induced fatty liver disease and further investigated the underlying mechanisms.…”

Differential Action of trans-10, cis-12 Conjugated Linoleic Acid on Adipocyte Differentiation of Ovine and 3T3-L1 Preadipocytes

“…Troglitazone, a PPAR-γ2 agonist, is an inducer and is essential for adipocyte differentiation in primary ovine preadipocytes, as reported previously (Roh et al, 2005). As trans-10, cis-12 CLA promotes ovine adipocyte differentiation, we investigated the direct effects of trans-10, cis-12 CLA on lipid accumulation and adipogenic gene expression in ovine preadipocytes under the supplementation of differentiation medium without a PPAR-γ2 agonist, troglitazone.…”

“…Total RNA from ovine preadipocytes and 3T3-L1 preadipocytes was isolated using Trizol Reagent (Gibco BRL, Rockville, MD). Semi-quantitative RT-PCR was performed to measure the levels of PPAR-γ2, adipophilin, and β-actin mRNA expression as previously described (Hong et al, 2005). β-Actin, the housekeeping gene, was used as an internal control.…”