Regulation of SRE‐mediated gene transcription by polyunsaturated triglyceride is as rapid and efficient as by free fatty acid

Sterol regulatory element binding proteins (SREBPs) are key transcription proteins that bind to sterol regulatory elements (SRE) of gene essential for cholesterol and fatty acid homeostasis. We previously demonstrated that polyunsaturated fatty acids (PUFA) strongly inhibit SREBP processing at post‐transcriptional levels. We now questioned if delivering PUFA as part of a triglyceride (TG) molecule would have similar effects and efficiency as free PUFA. CHO cells with a stably transfected 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) or VLDL‐sized trilinolein emulsions (TL, 25–200 μg/mL) in the presence and absence of apoE. Effects of LA and TL on decreasing SRE‐luciferase activity were both dose and time dependent and both TL and LA significantly and rapidly (<≤2–12 h) reduced SRE‐mediated gene expression by up to 75%. At equal estimated FA concentrations (0.15, 0.45 and 0.6 mM), SRE inhibition by TL was as effective as the LA effects. ApoE addition increased inhibition by TL to levels obtained with LA alone. The magnitude of gene suppression was highly correlated to cell TG mass, but neither TL nor LA had effects on SREBP‐1c mRNA expression. This study demonstrates that SRE‐mediated gene transcription is decreased both by free PUFA and TG‐derived PUFA and that apoE may contribute to inhibition of SRE‐mediated gene expression by enhancing TG derived FA uptake. We conclude that TG like FA are rapid and efficient modulators of SRE‐mediated gene expression and this can contribute to effect of post‐prandial lipemia on regulating whole body lipid metabolism.