title: Increased serum liver X receptor ligand oxysterols in patients with non-alcoholic fatty liver disease.
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.
authors.affiliation: Division of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami-machi, Inashiki-gun, Ibaraki 300-0395, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ikegami
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hyogo
authors.forename: Akira
authors.initials: A
authors.lastname: Honda
authors.forename: Teruo
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Tokushige
authors.forename: Etsuko
authors.initials: E
authors.lastname: Hashimoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Inui
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Susumu
authors.initials: S
authors.lastname: Tazuma
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D002853:Chromatography, Liquid; D005234:Fatty Liver / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D057093:Orphan Nuclear Receptors / Q000097:blood*; D011446:Prospective Studies; D011804:Quinolines / Q000627:therapeutic use*; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D011804:Quinolines; D002784:Cholesterol; C108475:pitavastatin