Role of adrenomedullin system in lipid metabolism and its signaling mechanism in cultured adipocytes
- 1 November 2008
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Vol. 295 (5), R1376-R1384
- https://doi.org/10.1152/ajpregu.90467.2008
Abstract
We investigated the levels of adrenomedullin (AM) system during the process of preadipocyte differentiation and its role in lipid metabolism and cellular signaling mechanism in differentiated adipocytes. We cultured rat preadipocytes and measured the following during the process of differentiation: two molecular forms of AM in the culture medium using a specific immunoradiometric assay and gene expression of AM and its receptor component using RT-PCR analysis. In differentiated adipocytes, we measured the effects of AM on the intracellular cAMP level, lipolysis, glucose incorporation, and the protein levels. Two molecular forms of AM were secreted into the medium, and the AM-mature/AM-total ratio was increased after 6 days of differentiation. Cultured rat preadipocytes highly expressed the genes of AM and its receptor components at day 1, and they increased at day 10. Administration of AM to preadipocytes increased the number of Oil Red O-positive adipocytes and spectrophotometric absorbance of Oil Red O. AM dose dependently increased cAMP level and lipolysis, and its effect was blocked by CGRP(8-37). Isoproterenol increased lipolysis, and AM had additive effects on isoproterenol-induced lipolysis. KT5720 and U0126 significantly inhibited the AM-induced lipolysis, whereas KT5720, but not U0126, significantly inhibited the isoproterenol-induced lipolysis. AM increased glucose incorporation and its effect was blocked by wortmannin. Western blot analysis revealed that AM increased phospho PKA, ERK, and Akt. These results indicate that AM and its receptor component are highly expressed in cultured adipocytes and may play a role in lipid metabolism via a different signaling pathway.Keywords
This publication has 38 references indexed in Scilit:
- Adrenomedullin Inhibits Adipogenesis Under Transcriptional Control of InsulinDiabetes, 2007
- Pathophysiologic and therapeutic implications of adrenomedullin in cardiovascular disordersPharmacology & Therapeutics, 2006
- The vasoactive peptide adrenomedullin is secreted by adipocytes and inhibits lipolysis through NO‐mediated β‐adrenergic agonist oxidationThe FASEB Journal, 2005
- Concomitant expression of adrenomedullin and its receptor components in rat adipose tissuesAmerican Journal of Physiology-Endocrinology and Metabolism, 2005
- Stimulation of Lipolysis and Hormone-sensitive Lipase via the Extracellular Signal-regulated Kinase PathwayJournal of Biological Chemistry, 2001
- Molecular forms of circulating adrenomedullin in patients with congestive heart failureJournal of Endocrinology, 1999
- Adrenomedullin Production in Fibroblasts: Its Possible Function as a Growth Regulator of Swiss 3T3 Cells*Endocrinology, 1998
- Regulation of Adrenomedullin Production in Rat Endothelial Cells1Endocrinology, 1998
- Possible role for gp160 in constitutive but not insulin-stimulated GLUT4 trafficking: dissociation of gp160 and GLUT4 localizationBiochemical Journal, 1998
- Plasma levels of adrenomedullin, a newly identified hypotensive peptide, in patients with hypertension and renal failure.JCI Insight, 1994