title: Autocrine/paracrine role of inflammation-mediated calcitonin gene-related peptide and adrenomedullin expression in human adipose tissue.
abstract: 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-1beta 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-1beta-mediated ProCT and CGRP secretion by 78 and 34%, respectively but augmented IL-1beta-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, TNFalpha, and IL-1beta 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.
authors.affiliation: Department of Research, University Hospitals, Hebelstrasse 20, 4031 Basel, Switzerland. philippe.linscheid@unibas.ch
authors.forename: Philippe
authors.initials: P
authors.lastname: Linscheid
authors.forename: Dalma
authors.initials: D
authors.lastname: Seboek
authors.forename: Henryk
authors.initials: H
authors.lastname: Zulewski
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keller
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology; D053607:Adrenomedullin; D019898:Autocrine Communication / Q000276:immunology; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000166:cytology; D019899:Paracrine Communication / Q000276:immunology; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D010455:Peptides; D012333:RNA, Messenger; D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide