title: Human C-reactive protein exacerbates metabolic disorders in association with adipose tissue remodelling.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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: Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors: Hidehiro
authors: H
authors: Kaneko
authors: Toshihisa
authors: T
authors: Anzai
authors: Toshiyuki
authors: T
authors: Nagai
authors: Atsushi
authors: A
authors: Anzai
authors: Toshiyuki
authors: T
authors: Takahashi
authors: Yoshinori
authors: Y
authors: Mano
authors: Kohkichi
authors: K
authors: Morimoto
authors: Yuichiro
authors: Y
authors: Maekawa
authors: Hiroshi
authors: H
authors: Itoh
authors: Tsutomu
authors: T
authors: Yoshikawa
authors: Satoshi
authors: S
authors: Ogawa
authors: Keiichi
authors: K
authors: Fukuda
mesh_terms: D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006439:Hemodynamics; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009929:Organ Size; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein; D048031:JNK Mitogen-Activated Protein Kinases