ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P521

Expression of adrenergic receptors and atrial natriuretic peptide in human adipose tissue of severe obese women and Rosiglitazone action during differentiation of human pre-adipocytes

Gabriella Garruti1, Vittorio Giusti3, Jurg Nussberger3, Christian Darimont4, Aline Appert-Collin2, Sebastiano Perrini1, Monique NennigerTosato2, Riccardo Giorgino1, Francesco Giorgino1 & Susanna Cotecchia2

1Department of Emergency and Organ Transplantation- Section of Internal Medicine, Endocrinology and Metabolic Diseases, University Medical School, Bari, Italy; 2Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland; 3Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; 4Nestlé Research Center, Lausanne, Switzerland.

Background: The balance between Adrenergic Receptor (AR) subtypes and Atrial Natriuretic Peptide (ANP) is crucial for lipolysis. It was previously demonstrated that ANP is strongly lipolytic and we recently demonstrated that ANP is expressed and secreted by human pre-adipocytes. In previous studies, β-receptor density and lipolysis were higher in human visceral adipose tissue (HVAT) as compared with human subcutaneous adipose tissue (HSAT).

Aims and Methods: The expression levels of ANP, AR subtypes and adipocyte differentiation markers (AdM) were analyzed by real-time RT-PCR in human subcutaneous (HSAT) and visceral (HVAT) fat biopsies from obese women and in a human pre-adipocytes cell line (ChubS7) during rosiglitazone-mediated differentiation.

Results: The expression of α2A-AR and β2-AR were higher in HSAT than in HVAT; α1A-AR, β1-AR and ANP expression were comparable, and α1B-AR, α1D-AR and β3-AR were not measurable in HVAT and HSAT. In both rosiglitazone- and non-stimulated Chub-S7 all AR subtypes, except for β3-AR, as well as ANP were expressed from day 3 to 6 of differentiation. At day 17, in rosiglitazone-stimulated Chub-S7, ANP was switched off, AdM and β3- AR were switched on, β2-AR increased, β1-AR was constantly low and α2A-AR significantly decreased as compared with basal.

Conclusions: Data on HVAT and HSAT suggest that both the pro-lipolytic β2-AR and the anti-lipolytic α2A-AR are involved in the balance between HVAT and HSAT accumulation. Data on ChubS7 demonstrate that β3-AR and AdM are simultaneously switched on during adipocyte differentiation. We suggest that at the end of the rosiglitazone-mediated differentiation, adipocytes require β3-AR-activation whereas the α2A-AR anti-lipolytic and ANP-mediated effects are decreased.