Regulation of human hepatocyte gene expression by fatty acids

被引:16
作者
Swagell, Christopher D.
Henly, Debra C.
Morris, C. Phillip
机构
[1] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Cooperat Res Ctr Diagnost, Brisbane, Qld 4059, Australia
[2] Bond Univ, Fac Med & Hlth Sci, Gold Coast, Qld 4229, Australia
关键词
glucokinase; gene expression; microarray analysis; saturated fatty acid; monounsaturated fatty acid; polyunsaturated fatty acid; palmitate; oleate; eicosapentaenoic acid; human hepatic cell line;
D O I
10.1016/j.bbrc.2007.07.191
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
It is known that fatty acids (FAs) regulate transcription through a number of FA responsive transcription factors. In order to investigate the effect of FAs on gene regulation in cultured human hepatocytes we examined the effect of palmitate on hepatic glucokinase (GK) promoter activity and expression of transcription factors that regulate GK expression. GK promoter activity was increased in constructs lacking a cAMP response element (CRE), while palmitate incubation decreased GK promoter activity in CRE-negative constructs. Cells exposed to palmitate showed increased levels of PPAR alpha apolipoprotein-AII and -B100 mRNA and decreased levels of SREBP-1c mRNA but there was no effect on LXR alpha and HNF-4 alpha mRNA. In addition, cDNA microarray analysis of short-term (1.5 h) transcriptional regulation by palmitate, oleate, and eicosapentaenoic acid (EPA) identified that oleate and EPA initiated similar changes in the pattern of hepatic gene regulation, whereas palmitate had little effect. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:374 / 380
页数:7
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