TitleDietary polyunsaturated fatty acids and regulation of gene transcription.
Publication TypeJournal Article
Year of Publication2002
AuthorsJump, DB
JournalCurr Opin Lipidol
Volume13
Issue2
Pagination155-64
Date Published2002 Apr
ISSN0957-9672
KeywordsBasic Helix-Loop-Helix Leucine Zipper Transcription Factors, CCAAT-Enhancer-Binding Proteins, Dietary Fats, Unsaturated, DNA-Binding Proteins, Fatty Acids, Unsaturated, Gene Expression Regulation, Hepatocyte Nuclear Factor 4, Humans, Liver X Receptors, Orphan Nuclear Receptors, Phosphoproteins, Receptors, Cytoplasmic and Nuclear, Sterol Regulatory Element Binding Protein 1, Transcription Factors, Transcription, Genetic
Abstract

Dietary polyunsaturated fatty acids (PUFAs) are a source of energy and structural components for cells. PUFAs also have dramatic effects on gene expression by regulating the activity or abundance of four families of transcription factor, including peroxisome proliferator activated receptor (PPAR) (alpha, beta and gamma), liver X receptors (LXRs) (alpha and beta), hepatic nuclear factor-4 (HNF-4)alpha and sterol regulatory element binding proteins (SREBPs) 1 and 2. These transcription factors play a major role in hepatic carbohydrate, fatty acid, triglyceride, cholesterol and bile acid metabolism. Non-esterified fatty acids or fatty acid metabolites bind to and regulate the activity of PPARs, LXRs and HNF-4. In contrast, PUFAs regulate the nuclear abundance of SREBPs by controlling the proteolytic processing of SREBP precursors, or regulating transcription of the SREBP-1c gene or turnover of mRNA(SREBP-1c). The n3 and n6 PUFAs are feed-forward activators of PPARs, while these same fatty acids are feedback inhibitors of LXRs and SREBPs. Saturated fatty acyl coenzyme A thioesters activate HNF-4 alpha, while coenzyme A thioesters of PUFAs antagonize HNF-4 alpha action. Understanding how fatty acids regulate the activity and abundance of these and other transcription factors will likely provide insight into the development of novel therapeutic strategies for better management of whole body lipid and cholesterol metabolism.

Alternate JournalCurr. Opin. Lipidol.
PubMed ID11891418
Grant ListR01 DK043220 / DK / NIDDK NIH HHS / United States
DK43220 / DK / NIDDK NIH HHS / United States