Human C-reactive protein exacerbates metabolic disorders in association with adipose tissue remodelling

Hidehiro Kaneko, Toshihisa Anzai, Toshiyuki Nagai, Atsushi Anzai, Toshiyuki Takahashi, Yoshinori Mano, Kohkichi Morimoto, Yuichiro Maekawa, Hiroshi Itoh, Tsutomu Yoshikawa, Satoshi Ogawa, Keiichi Fukuda

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)546-555
Number of pages10
JournalCardiovascular Research
Volume91
Issue number3
DOIs
Publication statusPublished - 2011 Aug 1

Fingerprint

High Fat Diet
C-Reactive Protein
Adipose Tissue
Transgenic Mice
Adiponectin
Insulin Resistance
Obesity
Macrophages
Diet
Chemokine CCL2
Mucins
Glucose Tolerance Test
Oils
Triglycerides
Fibrosis
Down-Regulation
Tumor Necrosis Factor-alpha
Hormones
Insulin
Staining and Labeling

Keywords

  • Biomarker
  • Cytokine
  • Inflammation
  • Insulin resistance
  • Macrophage
  • Obesity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Human C-reactive protein exacerbates metabolic disorders in association with adipose tissue remodelling. / Kaneko, Hidehiro; Anzai, Toshihisa; Nagai, Toshiyuki; Anzai, Atsushi; Takahashi, Toshiyuki; Mano, Yoshinori; Morimoto, Kohkichi; Maekawa, Yuichiro; Itoh, Hiroshi; Yoshikawa, Tsutomu; Ogawa, Satoshi; Fukuda, Keiichi.

In: Cardiovascular Research, Vol. 91, No. 3, 01.08.2011, p. 546-555.

Research output: Contribution to journalArticle

Kaneko, H, Anzai, T, Nagai, T, Anzai, A, Takahashi, T, Mano, Y, Morimoto, K, Maekawa, Y, Itoh, H, Yoshikawa, T, Ogawa, S & Fukuda, K 2011, 'Human C-reactive protein exacerbates metabolic disorders in association with adipose tissue remodelling', Cardiovascular Research, vol. 91, no. 3, pp. 546-555. https://doi.org/10.1093/cvr/cvr088
Kaneko, Hidehiro ; Anzai, Toshihisa ; Nagai, Toshiyuki ; Anzai, Atsushi ; Takahashi, Toshiyuki ; Mano, Yoshinori ; Morimoto, Kohkichi ; Maekawa, Yuichiro ; Itoh, Hiroshi ; Yoshikawa, Tsutomu ; Ogawa, Satoshi ; Fukuda, Keiichi. / Human C-reactive protein exacerbates metabolic disorders in association with adipose tissue remodelling. In: Cardiovascular Research. 2011 ; Vol. 91, No. 3. pp. 546-555.
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abstract = "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.",
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AU - Takahashi, Toshiyuki

AU - Mano, Yoshinori

AU - Morimoto, Kohkichi

AU - Maekawa, Yuichiro

AU - Itoh, Hiroshi

AU - Yoshikawa, Tsutomu

AU - Ogawa, Satoshi

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AB - 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.

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