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Dietary polyunsaturated fatty acids and hepatic gene expression

  • Fatty Acids, Related Compounds, And Gene Expression
  • Published:
Lipids

Abstract

Dietary polyunsaturated fatty acids (PUFA) have profound effects on hepatic gene transcription leading to significant changes in lipid metabolism. PUFA rapidly suppress transcription of genes encoding specific lipogenic and glycolytic enzymes and induce genes encoding specific peroxisomal and cytochrome P450 (CYP) enzymes. Using the peroxisome proliferator-activated receptor α (PPARα)-null mouse, we showed that dietary PUFA induction of acyl PPARα is not required for the PUFA-mediated suppression of fatty acid synthase (FAS), S14, or L-pyruvate kinase (L-PK). Studies in primary rat hepatocytes and cultured 3T3-L1 adipocytes showed that metabolites of 20:4n-6, like prostaglandin E2 (PGE2), suppress mRNA encoding FAS, S14, and L-PK through a Gi/Go-coupled signal transduction cascade. In contrast to adipocytes, 20:4n-6-mediated suppression of lipogenic gene expression in hepatic parenchymal cells does not require cyclooxygenase. Transfection analysis of S14CAT fusion genes in primary hepatocytes shows that peroxisome proliferator-activated PPARα acts on the thyroid hormone response elements (−2.8/−2.5 kb). In contrast, both PGE2 and 20:4n-6 regulate factors that act on the proximal promoter (−150/−80 bp) region, respectively. In conclusion, PUFA affects hepatic gene transcription through at least three distinct mechanisms: (i) a PPAR-dependent pathway, (ii) a prostanoid pathway, and (iii) a PPAR and prostanoid-independent pathway. PUFA regulation of hepatic lipid metabolism involves an integration of these multiple pathways.

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Abbreviations

AOX:

acyl CoA oxidase

CYP:

cytochrome P450

Fa-CoA:

fatty acid CoA

FAS:

fatty acid synthase

L-PK:

L-pyruvate kinase

PPAR:

peroxisome proliferator activated receptor

PUFA:

polyunsaturated fatty acids

RR:

regulatory region

S14:

S14 protein

T3 :

triodothyronine

VLDL:

very low density lipoprotein

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Authors and Affiliations

  1. Departments of Physiology, Biochemistry, and Animal Science, Michigan State University, 48824, East Lansing, Michigan

    Donald B. Jump, Annette Thelen & Michelle Mater

Authors
  1. Donald B. Jump
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  2. Annette Thelen
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  3. Michelle Mater
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Corresponding author

Correspondence to Donald B. Jump.

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Jump, D.B., Thelen, A. & Mater, M. Dietary polyunsaturated fatty acids and hepatic gene expression. Lipids 34 (Suppl 1), S209–S212 (1999). https://doi.org/10.1007/BF02562292

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