| C1q/TNF-related protein-3 represents a novel and endogenous lipopolysaccharide antagonist of the adipose tissue. | |
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MedLine Citation:
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PMID: 20739398 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Andrea Kopp; Margarita Bala; Christa Buechler; Werner Falk; Philipp Gross; Markus Neumeier; Jürgen Schölmerich; Andreas Schäffler |
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Publication Detail:
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Type: Journal Article Date: 2010-08-25 |
Journal Detail:
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Title: Endocrinology Volume: 151 ISSN: 1945-7170 ISO Abbreviation: Endocrinology Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-21 Completed Date: 2010-11-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 5267-78 Citation Subset: AIM; IM |
Affiliation:
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Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3T3-L1 Cells Adipocytes / drug effects, metabolism* Adipose Tissue / drug effects, metabolism* Adult Animals Blotting, Western Chemokine CCL2 / metabolism Cytokines / metabolism Diabetes Mellitus, Type 2 / metabolism* Enzyme-Linked Immunosorbent Assay Female Humans Inflammation / metabolism* Lipopolysaccharides / pharmacology Male Mice Middle Aged Monocytes / drug effects, metabolism RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / drug effects, physiology Toll-Like Receptors / metabolism Transfection Tumor Necrosis Factors / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/C1QTNF3 protein, human; 0/Chemokine CCL2; 0/Cytokines; 0/Lipopolysaccharides; 0/RNA, Messenger; 0/Toll-Like Receptors; 0/Tumor Necrosis Factors |
| Comments/Corrections | |
Comment In:
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Endocrinology. 2010 Nov;151(11):5095-7
[PMID:
20962058
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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