Dietary polyunsaturated fatty acid regulation of hepatic gene transcription

Abstract

Objective: Dietary polyunsaturated fatty acids have a significant impact on the activity and abundance of key transcription factors controlling the expression of proteins involved in major metabolic pathways. The primary objective of this review is to provide an overview of our understanding of how dietary PUFA effects on gene expression lead to changes in hepatic metabolism. Design: Narrative review. This review will focus on how dietary PUFA control hepatic lipid synthesis and oxidation through the regulation of specific transcription factors. Research articles that address critical issues in fatty acid regulation of gene expression were identified. Information from these papers is summarized. Results: Four families of hepatic transcription factors have been identified that are regulated by changes in dietary lipid intake or by treating cultured cells with specific fatty acids. These families include: peroxisome proliferator activated receptors (PPARa, b, g1, g2 ), liver X receptors (LXRa and b), hepatic nuclear factor-4 a (HNF-4a) and sterol regulatory element binding protein (SREBP-1a, -1c and –2). Together, these factors control carbohydrate and lipid metabolism, cholesterol and bile acid metabolism and apolipoproteins production. Conclusions: These studies reveal a complex interaction between dietary lipid, specific transcription factors and hepatic carbohydrate, lipid, cholesterol and bile acid metabolism. Keywords: PPAR, LXR, HNF4, SREBP, PUFA, Transcription