Document Detail

C1q/TNF-related protein-3 represents a novel and endogenous lipopolysaccharide antagonist of the adipose tissue.
MedLine Citation:
PMID:  20739398     Owner:  NLM     Status:  MEDLINE    
Proteins secreted by adipocytes (adipokines) play an important role in the pathophysiology of type 2 diabetes mellitus and the associated chronic and low-grade state of inflammation. It was the aim to characterize the antiinflammatory potential of the new adipocytokine, C1q/TNF-related protein-3 (CTRP-3), which shows structural homologies to the pleiotropic adipocytokine adiponectin. mRNA and protein expression of CTRP-3 was analyzed by RT-PCR and Western blot. Recombinant CTRP-3 and small interfering RNA-based strategies were used to investigate the effect of CTRP-3 on toll-like receptor (TLR) ligand, lipopolysaccharide (LPS)-, and lauric acid-induced chemokine release of monocytes and adipocytes. Together with complex ELISA-based techniques, a designed TLR4/myeloid differentiation protein-2 fusion molecule shown to bind LPS was used to prove the ability of CTRP-3 to act as endogenous LPS antagonist. CTRP-3 is synthesized in monocytes and adipocytes. The recombinant protein dose-dependently inhibits the release of chemokines in monocytes and adipocytes that were induced by lauric acid, LPS, and other TLR ligands in vitro and ex vivo. CTRP-3 inhibits monocyte chemoattractant protein-1 release in adipocytes, whereas small interfering RNA-mediated knockdown of CTRP-3 up-regulates monocyte chemoattractant protein-1 release, reduces lipid droplet size, and decreases intracellular triglyceride concentration in adipocytes, causing a dedifferentiation into a more proinflammatory and immature phenotype. By using a designed TLR4/MD-2 fusion molecule, it is shown by different techniques that CTRP-3 specifically and effectively inhibits the binding of LPS to its receptor, TLR4/MD-2. CTRP-3 inhibits three basic and common proinflammatory pathways involved in obesity and type 2 diabetes mellitus (adipo-inflammation) by acting as an endogenous LPS antagonist of the adipose tissue.
Andrea Kopp; Margarita Bala; Christa Buechler; Werner Falk; Philipp Gross; Markus Neumeier; Jürgen Schölmerich; Andreas Schäffler
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Publication Detail:
Type:  Journal Article     Date:  2010-08-25
Journal Detail:
Title:  Endocrinology     Volume:  151     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-21     Completed Date:  2010-11-04     Revised Date:  2013-05-23    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5267-78     Citation Subset:  AIM; IM    
Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany.
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MeSH Terms
3T3-L1 Cells
Adipocytes / drug effects,  metabolism*
Adipose Tissue / drug effects,  metabolism*
Blotting, Western
Chemokine CCL2 / metabolism
Cytokines / metabolism
Diabetes Mellitus, Type 2 / metabolism*
Enzyme-Linked Immunosorbent Assay
Inflammation / metabolism*
Lipopolysaccharides / pharmacology
Middle Aged
Monocytes / drug effects,  metabolism
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects,  physiology
Toll-Like Receptors / metabolism
Tumor Necrosis Factors / metabolism*
Reg. No./Substance:
0/C1QTNF3 protein, human; 0/Chemokine CCL2; 0/Cytokines; 0/Lipopolysaccharides; 0/RNA, Messenger; 0/Toll-Like Receptors; 0/Tumor Necrosis Factors
Comment In:
Endocrinology. 2010 Nov;151(11):5095-7   [PMID:  20962058 ]
Erratum In:
Endocrinology. 2013 Apr;154(4):1667

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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