Increased serum liver X receptor ligand oxysterols in patients with non-alcoholic fatty liver disease

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• 作者：Tadashi Ikegami (1)
  Hideyuki Hyogo (3)
  Akira Honda (1) (2)
  Teruo Miyazaki (2) (5)
  Katsutoshi Tokushige (6)
  Etsuko Hashimoto (6)
  Kazuo Inui (7)
  Yasushi Matsuzaki (1) (5)
  Susumu Tazuma (4)
  
• 关键词：NAFLD ; Cholesterol metabolism ; Oxysterol ; Bile acids
• 刊名：Journal of Gastroenterology
• 出版年：2012
• 出版时间：November 2012
• 年：2012
• 卷：47
• 期：11
• 页码：1257-1266
• 全文大小：521KB
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• 作者单位：Tadashi Ikegami (1)
  Hideyuki Hyogo (3)
  Akira Honda (1) (2)
  Teruo Miyazaki (2) (5)
  Katsutoshi Tokushige (6)
  Etsuko Hashimoto (6)
  Kazuo Inui (7)
  Yasushi Matsuzaki (1) (5)
  Susumu Tazuma (4)
  
  1. Division of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami-machi, Inashiki-gun, Ibaraki, 300-0395, Japan
  3. Department of Medicine and Molecular Science, Graduate School of Biochemical Science, Hiroshima University, Hiroshima, Japan
  2. Center for Collaborative Research, Tokyo Medical University Ibaraki Medical Center, Inashiki-gun, Japan
  5. Department of Development for Community Medicine, Tokyo Medical University, Tokyo, Japan
  6. Department of Medicine and Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan
  7. Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Japan
  4. Department of General Medicine, Graduate School of Biochemical Science, Hiroshima University, Hiroshima, Japan
  
• ISSN：1435-5922

文摘

Background This study is a post-hoc analysis of a subset of patients who participated in our multi-institutional case-control study that evaluated the effects of pitavastatin in patients with non-alcoholic fatty liver disease (NAFLD) with hypercholesterolemia. Methods Serum samples of fifteen patients with biopsy-proven NAFLD with dyslipidemia were investigated. Serum markers of lipid metabolism were quantified by liquid chromatography-mass spectrometry (LC–MS)/MS. These data were then compared with those of 36 sex- and age-matched healthy controls. In addition, changes in these markers produced by treatment with pitavastatin were evaluated. Results Serum non-cholesterol sterols, reflecting intestinal cholesterol absorption, were significantly lower in the NAFLD patients compared to the controls, and the cholesterol synthesis marker, the ratio of lathosterol to cholesterol, was not significantly different between the two groups. Serum proportions of liver X receptor α (LXRα) ligand oxysterols (ratios to cholesterol) were significantly elevated in the NAFLD patients compared to the controls. The sum of oxysterols relative to cholesterol and the homeostasis model assessment as an index of insulin resistance (HOMA-IR) were significantly correlated. The marker representing cholesterol synthesis was significantly suppressed by pitavastatin treatment, from 3?months after initiation of the treatment, and the suppression remained significant during the observation period. The markers representing cholesterol absorption were unchanged at 3?months, but had significantly increased at 12?months. Serum oxysterol levels relative to cholesterol maintained high values and did not change significantly during the 12-month period of treatment. Conclusions: We speculate that serum LXRα ligand oxysterol levels (relative to cholesterol) could be surrogate markers of insulin resistance, and that high oxysterol levels in the circulation may play an important role in the development of hepatic and peripheral insulin resistance followed by NAFLD.