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Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats.

Abstract：

AIMS:Second-generation antipsychotic drugs (SGAs) have a high risk for serious metabolic side-effects including dyslipidemia. This study aimed to investigate the acute effects of oral olanzapine treatment on the expression of genes for fatty acid and cholesterol biosynthesis in rats. MAIN METHODS:Female Sprague-Dawley rats were treated orally with olanzapine (1mg/kg, equivalent to a human clinical dose of 10mg) via self-administration aimed to measure pharmacokinetics. Based on the pharmacokinetic analysis, the acute effects of olanzapine on sterol regulatory element binding protein (SREBP)-related fatty acid/cholesterol metabolism genes were investigated in the liver and perirenal white adipose tissue (WAT) by Real-time quantitative PCR. KEY FINDINGS:A pharmacokinetic analysis demonstrated that the maximum concentration of olanzapine in plasma (Cmax) occurred at 6h with a peak concentration of 276.5ng/ml after a single oral treatment and with a plasma elimination half-life of 3.5h after peak. The mRNA expression of SREBP-2 and target genes for cholesterol synthesis and transport was increased 1.9 8.8 fold compared with the control at 6h after olanzapine administration but returned to basal level at 12h post-treatment, while the increased mRNA expression of SREBP-1c and its targeted fatty acid-related genes appeared at both 6h and 12h post-treatment. SIGNIFICANCE:The present study provided evidence that olanzapine at a clinically-relevant dose caused abnormal expression of genes involved in lipid metabolism in the liver and WAT. These results suggest that olanzapine may cause dyslipidemia side-effects through direct effects on lipid biosynthesis and efflux genes associated with SREBP-stimulated transcriptional changes.

journal_name

Life Sci

journal_title

Life sciences

authors

Liu X,Deng C,Cao S,Gong J,Wang BC,Hu CH

doi

10.1016/j.lfs.2015.01.033

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

72-8

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(15)00102-2

journal_volume

128

pub_type

杂志文章

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