Document Detail


Human C-reactive protein exacerbates metabolic disorders in association with adipose tissue remodelling.
MedLine Citation:
PMID:  21447704     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: C-reactive protein (CRP) expression is increased with metabolic alterations. We sought to clarify the effect of CRP on the development of obesity-induced metabolic disorders using human CRP-overexpressing transgenic mice (CRPTG).
METHODS AND RESULTS: CRPTG and their non-transgenic littermates (CON) were fed a standard diet (STD) or a high-fat diet (HFD) from 6 weeks of age. Oral glucose tolerance and intraperitoneal insulin tolerance tests 12 weeks after starting the diets showed deterioration of glucose tolerance and insulin sensitivity in HFD/CRPTG compared with HFD/CON. Hepatocellular ballooning, oil droplets, and peri-sinusoidal fibrosis were more prominent in HFD/CRPTG than in HFD/CON. In HFD/CRPTG, hepatic triglyceride content was higher and serum adiponectin levels lower than in HFD/CON. Epididymal adipose tissue mRNA expression of mucin-like, hormone receptor-like 1, monocyte chemotactic protein-1, and tumour necrosis factor-α in HFD/CRPTG was up-regulated compared with that in HFD/CON. Immunohistochemical staining of epididymal adipose tissue showed that the number of Mac-3(+) macrophages was higher in HFD/CRPTG than in HFD/CON.
CONCLUSION: Human CRP overexpression facilitated the development of insulin resistance and hepatosteatosis with HFD in association with adiponectin down-regulation and enhancement of macrophage infiltration and expression of pro-inflammatory cytokines in epididymal adipose tissue, suggesting its pathogenic role in the development of obesity-induced metabolic disorders.
Authors:
Hidehiro Kaneko; Toshihisa Anzai; Toshiyuki Nagai; Atsushi Anzai; Toshiyuki Takahashi; Yoshinori Mano; Kohkichi Morimoto; Yuichiro Maekawa; Hiroshi Itoh; Tsutomu Yoshikawa; Satoshi Ogawa; Keiichi Fukuda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-29
Journal Detail:
Title:  Cardiovascular research     Volume:  91     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-20     Completed Date:  2011-11-23     Revised Date:  2012-04-09    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  546-55     Citation Subset:  IM    
Affiliation:
Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adiponectin / blood
Adipose Tissue / metabolism*
Animals
Biological Markers / blood
Blood Glucose / metabolism
Body Weight
C-Reactive Protein / genetics,  metabolism*
Disease Models, Animal
Fatty Liver / genetics,  metabolism*,  physiopathology
Gene Expression Regulation
Glucose Intolerance / genetics,  metabolism*,  physiopathology
Glucose Tolerance Test
Hemodynamics
Humans
Insulin / blood
Insulin Resistance
JNK Mitogen-Activated Protein Kinases / metabolism
Lipids / blood
Liver / metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Obesity / complications,  genetics,  metabolism*,  physiopathology
Organ Size
Serum Amyloid A Protein / metabolism
Time Factors
Up-Regulation
Chemical
Reg. No./Substance:
0/Adiponectin; 0/Adipoq protein, mouse; 0/Biological Markers; 0/Blood Glucose; 0/Insulin; 0/Lipids; 0/Serum Amyloid A Protein; 9007-41-4/C-Reactive Protein; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases

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


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