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Endocrinology, doi:10.1210/en.2004-1424
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Endocrinology Vol. 146, No. 6 2699-2708
Copyright © 2005 by The Endocrine Society

Autocrine/Paracrine Role of Inflammation-Mediated Calcitonin Gene-Related Peptide and Adrenomedullin Expression in Human Adipose Tissue

Philippe Linscheid1, Dalma Seboek1, Henryk Zulewski, Ulrich Keller and Beat Müller

Departments of Research (P.L., D.S., H.Z., U.K., B.M.) and Endocrinology, Diabetology, and Clinical Nutrition (H.Z., U.K., B.M.), University Hospital, CH-4031 Basel, Switzerland

Address all correspondence and requests for reprints to: Philippe Linscheid, Ph.D., Department of Research, University Hospitals, Hebelstrasse 20, 4031 Basel, Switzerland. E-mail: philippe.linscheid{at}unibas.ch.

Human adipose tissue is a contributor to inflammation- and sepsis-induced elevation of serum procalcitonin (ProCT). Several calcitonin (CT) peptides, including ProCT, CT gene-related peptide (CGRP), and adrenomedullin (ADM) are suspected mediators in human inflammatory diseases. Therefore, we aimed to explore the expression, interactions, and potential roles of adipocyte-derived CT peptide production. Expression of CT peptide-specific transcripts was analyzed by RT-PCR and quantitative real-time PCR in human adipose tissue biopsies and three different inflammation-challenged human adipocyte models. ProCT, CGRP, and ADM secretions were assessed by immunological methods. Adipocyte transcriptional activity, glycerol release, and insulin-mediated glucose transport were studied after exogenous CGRP and ADM exposure. With the exception of amylin, CT peptides were expressed in adipose tissue biopsies from septic patients, inflammation-activated mature explanted adipocytes, and macrophage-activated preadipocyte-derived adipocytes. ProCT and CGRP productions were significantly augmented in IL-1ß and lipopolysaccharide-challenged mesenchymal stem cell-derived adipocytes but not in undifferentiated mesenchymal stem cells. In contrast, ADM expression occurred before and after adipogenic differentiation. Interferon-{gamma} coadministration inhibited IL-1ß-mediated ProCT and CGRP secretion by 78 and 34%, respectively but augmented IL-1ß-mediated ADM secretion by 50%. Exogenous CGRP and ADM administration induced CT, CGRP I, and CGRP II mRNAs and dose-dependently (10–10 and 10–6 M) enhanced glycerol release. In contrast, no CGRP- and ADM-mediated effects were noted on ADM, TNF{alpha}, and IL-1ß mRNA abundances. In summary, CGRP and ADM are two differentially regulated novel adipose tissue secretion factors exerting autocrine/paracrine roles. Their lipolytic effect (glycerol release) suggests a metabolic role in adipocytes during inflammation.




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