Regulation of human hepatocyte gene expression by fatty acids.
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 PPARalpha apolipoprotein-AII and -B100 mRNA and decreased levels of SREBP-1c mRNA but there was no effect on LXRalpha and HNF-4alpha mRNA. In addition, cDNA microarray analysis of short-term (1.5h) 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.
Swagell
Christopher D
CD
Cooperative Research Centre for Diagnostics, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld 4059, Australia.
Henly
Debra C
DC
Morris
C Phillip
CP
D000818:Animals; D016633:Apolipoprotein A-II / Q000235:genetics; D053299:Apolipoprotein B-100 / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D005941:Glucokinase / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D047493:PPAR alpha / Q000235:genetics; D010168:Palmitates / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D014162:Transfection
D016633:Apolipoprotein A-II; D053299:Apolipoprotein B-100; D047493:PPAR alpha; D010168:Palmitates; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D019301:Oleic Acid; D015118:Eicosapentaenoic Acid; D000242:Cyclic AMP; D008156:Luciferases; D005941:Glucokinase