Direct stimulatory effect of Ghrelin on Leptin production by rat peri-renal adipocytes in culture.

J. PIERMARIA, A. GIOVAMBATTISTA, MARÍA O. SUESCUM, RICARDO S. CALANDRA AND E. SPINEDI.

New Orleans, USA

Congreso; Annual Meeting of the American Endocrine Society; 2004

American Endocrine Society

Title: Direct stimulatory effect of ghrelin on leptin production by rat peri-renal adipocytes in culture. Judith Piermaria 1,  Andres Giovambattista 1, Maria O Suescun 1, Ricardo S Calandra1 and Eduardo Spinedi 2 . 1Reproductive Endocrinology, IMBICE, La Plata, Buenos Aires, Argentina, 1900 and 2Neuroendocrine Unit, IMBICE, La Plata, Buenos Aires, Argentina. Ghrelin, a peripheral orexigenic signal, plays an important role in body homeostasis by cooperating with other peripheral and hypothalamic systems to control integrated activity of the appetite/satiety circuitry. Although more extensive studies on the hypothalamic effects of ghrelin on energy metabolism have been performed, peripheral actions of ghrelin are less explored up the present time. Besides its in vivo adipogenic effect (1,2) and inhibitory activity on adiponectin (3) and resistin (2) production at adipose tissue level, up to now, no studies have been reported on a direct role of ghr in adipocyte function. Thus, the present study was designed to test whether ghrelin exerts any direct effect on white adipose tissue leptin production. For this aim, adipocytes from rat (adult male Fischer 344 rats) peri-renal fat pads were, mechanically/enzimatically, dispersed and isolated adipocytes (105 cells/well) were cultured in the absence (baseline) or presence of ghrelin. The results indicated that ghrelin (when tested at 0.1 nM) was able to enhance leptin release over the respective baseline after 12, 24 and 48 h culture; however, 0.1 ghrelin-induced leptin secretion optimal after 24 h culture. Thereafter, 24 h-incubated adipocytes without or with several ghrelin concentrations (0.001-1 nM) showed a concentration-related response, in terms of leptin output into the incubation medium, to the GH secretagogue stimulus. Finally adipocytes were incubated for 24 h with 0.1 nM ghrelin in the absence or presence of different concentrations (10, 100 and 1,000 nM) of the, low affinity, ghrelin inverse agonist (Arg1-Phe5 -Trp7, 9-Leu11-Substance P) (4); the results indicated that the stimulatory effect of ghrelin (0.1 nM) on leptin secretion by adipocytes was fully abolished in the presence of the middle and highest ghrelin inverse agonist concentrations. Thus our data strongly support that ghrelin exerts a direct, specific, secretagogue effect on peri-renal adipocyte leptin release; thus indicating that ghrelin is able to modulate the production of several, white fat-derived, adipokines. This observation further suggests that the results of the interaction ghrelin-leptin could play an important modulatory role for mantaining homeostasis. References: 1. Choi K, Roh SG, Hong YH, Shrestha YB, Hishikawa D, Chen C, Kojima M, Kangawa, K, Sasaki S. The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis. Endocrinology 2003; 144:754-759. 2. Asakawa A, Inui A, Kaga T, Katsuura G, Fujimiya M, Fujino MA, Kasuga M. Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 2003;52:947-952. 3. Ott V, Fasshauer M, Dalski A, Meier B, Perwitz N, Klein HH, Tschop M, Klein J. Direct peripheral effects of ghrelin include suppression of adiponectin expression. Horm Metab Res 2002;34:640-645. 4. Holst B, Cygankiewicz A, Jensen TH Ankersen M, Schwartz TW. High constitutive signaling of the ghrelin receptor-identification of a poteflt inverse agonist. Mol Endocrinol 2003;17:2201-2210. Financial Support: Beca Carrillo-Onatiltivia 2003 and PICT 5/5191/99 (to E.S.)