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01.11.2012 | Original Article—Liver, Pancreas, and Biliary Tract

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

verfasst von: Tadashi Ikegami, Hideyuki Hyogo, Akira Honda, Teruo Miyazaki, Katsutoshi Tokushige, Etsuko Hashimoto, Kazuo Inui, Yasushi Matsuzaki, Susumu Tazuma

Erschienen in: Journal of Gastroenterology | Ausgabe 11/2012

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Abstract

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.

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Titel: Increased serum liver X receptor ligand oxysterols in patients with non-alcoholic fatty liver disease
verfasst von: Tadashi Ikegami
Hideyuki Hyogo
Akira Honda
Teruo Miyazaki
Katsutoshi Tokushige
Etsuko Hashimoto
Kazuo Inui
Yasushi Matsuzaki
Susumu Tazuma
Publikationsdatum: 01.11.2012
Verlag: Springer Japan
Erschienen in: Journal of Gastroenterology / Ausgabe 11/2012
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-012-0585-0

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