Fatty acid supplied as triglyceride regulates SRE-mediated gene expression as efficiently as free fatty acids.
Sterol regulatory element binding proteins (SREBPs) are key transcription proteins that bind to sterol regulatory elements (SRE) of genes essential for cellular cholesterol and fatty acid homeostasis. Polyunsaturated fatty acids (PUFA) strongly inhibit SREBP processing at post-transcriptional levels. We questioned if delivering PUFA as part of a triglyceride (TG) molecule would have similar effects and efficiency as free non-esterified PUFA. CHO cells stably transfected with an SRE-promoter linked to the luciferase reporter gene were incubated for 8-24 h with linoleic acid (LA) complexed to BSA (molar ratios 0.5-4:1), VLDL-sized trilinolein emulsions (TL, 25-200 microg/ml), and chylomicron-sized soy oil emulsions in the presence and absence of apoE. Effects of LA and TL on decreasing SRE-luciferase activity were similar and dose and time dependent. Both TL and LA significantly and rapidly (<or=2-12 h) reduced SRE-mediated gene expression by up to 75%. At equal fatty acid concentrations, SRE inhibition by TL was as effective as LA. ApoE addition increased inhibition by TL. Inhibition of gene expression was highly correlated to cell TG accumulation. We conclude that TG like fatty acids are rapid and efficient modulators of SRE-mediated gene expression.
Densupsoontorn
Narumon
N
Institute of Human Nutrition and Department of Pediatrics, College of Physicians and Surgeons, Columbia University, 630 W. 168th St., PH1512, New York, NY 10032, USA.
Worgall
Tilla S
TS
Seo
Toru
T
Hamai
Hiroko
H
Deckelbaum
Richard J
RJ
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D017930:Genes, Reporter; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D050436:Regulatory Elements, Transcriptional; D051779:Sterol Regulatory Element Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism*; D014162:Transfection; D014280:Triglycerides / Q000494:pharmacology*
D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D051779:Sterol Regulatory Element Binding Proteins; D013261:Sterols; D014280:Triglycerides