Des-n-Octanoyl Ghrelin-induced adipogenesis and leptin production

GIOVAMBATTISTA, A; ALZAMENDI, A; GAILLARD, R; SPINEDI, E

New Orleans , USA

Congreso; 2007 Annual Scientific Meeting of NAASO; 2007

The Obesity Society

Ghrelin gene-derived peptides modulate food intake and adipogenesis in vivo. Although Des-n-octanoyl (Des-Acyl) Ghrelin is the major Ghrelin form in circulation, it does not stimulate food intake after peripheral administration in rodents. The aim of this study was to explore whether Des-Acyl Ghrelin could modulate, in vitro, preadipocyte differentiation and adipocyte function. First, fibroblastic preadipocytes from retroperitoneal (RP) fat pads of adult male rats were classically induced to differentiation in culture for 8 days, with or without Des-Acyl Ghrelin. Then, adipocytes obtained 8 days after RP preadipocyte differentiation, were incubated for 12 h with or without Des-Acyl Ghrelin, combined or not with either inhibitors of protein synthesis, insulin or GHS-R1a antagonist. Our data indicate that Des-Acyl Ghrelin facilitated RP preadipocyte differentiation (enhanced cell lipid content, Fig. 1, and PPARÎ?2 and LPL mRNAs expression) at 1 nM concentration or more. We also found that Des-Acyl Ghrelin (0.1-10 nM) had direct leptin-releasing activity on RP adipocytes, and significantly enhanced adipocyte ob mRNA expression. The leptin releasing activity of Des-Acyl Ghrelin was similar to and lower than those found with insulin and Ghrelin, respectively. Des-Acyl Ghrelin-induced adipocyte leptin production was prevented by inhibitors of protein synthesis but not by GHS-R1a antagonist (Fig. 2). Finally, Des-Acyl Ghrelin enhanced medium glucose consumption by adipocytes in culture. This study provides evidence for a direct and positive modulation of rat adipogenesis and adipocyte function by Des-Acyl Ghrelin, although via a GHS-R1a unrelated mechanism.