Fetuin-A negatively correlates with liver and vascular fibrosis in nonalcoholic fatty liver disease subjects

Authors

  • Motoya Sato,

    1. Department of Molecular Biochemistry & Clinical Investigation, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
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    • These authors contributed equally to this study.
  • Yoshihiro Kamada,

    1. Department of Molecular Biochemistry & Clinical Investigation, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
    2. Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
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    • These authors contributed equally to this study.
  • Yuri Takeda,

    1. Department of Molecular Biochemistry & Clinical Investigation, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
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  • Sachiho Kida,

    1. Department of Molecular Biochemistry & Clinical Investigation, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
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  • Yuka Ohara,

    1. Department of Molecular Biochemistry & Clinical Investigation, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
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  • Hironobu Fujii,

    1. Department of Molecular Biochemistry & Clinical Investigation, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
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  • Maaya Akita,

    1. Department of Molecular Biochemistry & Clinical Investigation, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
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  • Kayo Mizutani,

    1. Department of Molecular Biochemistry & Clinical Investigation, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
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  • Yuichi Yoshida,

    1. Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
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  • Makoto Yamada,

    1. aMs New Otani Clinic, Osaka, Osaka, Japan
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  • Hidetaka Hougaku,

    1. Nara Institute of Science and Technology, Ikoma, Nara, Japan
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  • Tetsuo Takehara,

    1. Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
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  • Eiji Miyoshi

    Corresponding author
    1. Department of Molecular Biochemistry & Clinical Investigation, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
    • Correspondence

      Eiji Miyoshi, MD, PhD, Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita, Osaka 565-0871, Japan

      Tel: +81-6-6879-2590

      Fax: +81-6-6879-2590

      e-mail: emiyoshi@sahs.med.osaka-u.ac.jp

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Abstract

Background & Aims

Fetuin-A (α2HS-glycoprotein), a liver secretory glycoprotein, is known as a transforming growth factor (TGF)-β1 signalling inhibitor. Serum fetuin-A concentration is associated with nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease. However, the usefulness of serum fetuin-A as a predictive fibrosis biomarker in NAFLD patients remains unclear. In this study, we investigated the relationship between circulating fetuin-A levels and fibrosis-related markers [platelet count, NAFLD fibrosis score and carotid intima media thickness (IMT)] in subjects with NAFLD.

Methods

A total of 295 subjects (male, 164; female, 131) who received medical health check-ups were enrolled in this study. NAFLD was diagnosed using abdominal ultrasonography. Serum fetuin-A was measured by ELISA. IMT was assessed using a high-resolution ultrasound scanner. Using recombinant human fetuin-A, we investigated the effects of fetuin-A on hepatic stellate cells, which play a pivotal role in the process of hepatic fibrosis.

Results

Serum fetuin-A concentration was significantly correlated with platelet count (R = 0.19, < 0.01), NAFLD fibrosis score (R = −0.25, P < 0.01) and mean IMT (R = −0.22, < 0.01). Multivariate analyses revealed that the fetuin-A concentration is a significant and independent determinant of platelet count, NAFLD fibrosis score and mean IMT. Recombinant fetuin-A suppressed TGF-β1 signalling and fibrosis-related gene expression and increased the expression of TGF-β1 pseudoreceptor bone morphogenic protein and activin membrane-bound inhibitor (BAMBI).

Conclusions

Serum fetuin-A level is associated with liver/vessel fibrosis-related markers in NAFLD patients. Circulating fetuin-A could be a useful serum biomarker for predicting liver and vascular fibrosis progression in NAFLD patients.

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