Autocrine/paracrine role of inflammation-mediated calcitonin gene-related peptide and adrenomedullin expression in human adipose tissue

Endocrinology. 2005 Jun;146(6):2699-708. doi: 10.1210/en.2004-1424. Epub 2005 Mar 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / immunology
  • Adipocytes / metabolism*
  • Adipose Tissue / cytology
  • Adipose Tissue / immunology
  • Adrenomedullin
  • Autocrine Communication / immunology
  • Calcitonin Gene-Related Peptide / genetics
  • Calcitonin Gene-Related Peptide / immunology*
  • Cells, Cultured
  • Coculture Techniques
  • Gene Expression Regulation / immunology
  • Humans
  • Macrophages / cytology
  • Paracrine Communication / immunology
  • Peptides / genetics*
  • Peptides / metabolism
  • RNA, Messenger / analysis
  • Sepsis / immunology*
  • Sepsis / metabolism*
  • Sepsis / physiopathology


  • Peptides
  • RNA, Messenger
  • Adrenomedullin
  • Calcitonin Gene-Related Peptide