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Graduate Program of Nutrition and the Institute of Cell and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712
3To whom correspondence should be addressed at 115 Gearing Building, The University of Texas, Austin, TX 78712. E-mail: stevedclarke{at}mail.utexas.edu
This review addresses the hypothesis that polyunsaturated fatty acids
(PUFA), particularly those of the (n-3) family, play pivotal roles as
"fuel partitioners" in that they direct fatty acids away from
triglyceride storage and toward oxidation, and that they enhance
glucose flux to glycogen. In doing this, PUFA may protect against the
adverse symptoms of the metabolic syndrome and reduce the risk of heart
disease. PUFA exert their beneficial effects by up-regulating the
expression of genes encoding proteins involved in fatty acid oxidation
while simultaneously down-regulating genes encoding proteins of
lipid synthesis. PUFA govern oxidative gene expression by activating
the transcription factor peroxisome proliferator-activated receptor
. PUFA suppress lipogenic gene expression by reducing the nuclear
abundance and DNA-binding affinity of transcription factors
responsible for imparting insulin and carbohydrate control to lipogenic
and glycolytic genes. In particular, PUFA suppress the nuclear
abundance and expression of sterol regulatory element binding protein-1
and reduce the DNA-binding activities of nuclear factor Y, Sp1 and
possibly hepatic nuclear factor-4. Collectively, the studies discussed
suggest that the fuel "repartitioning" and gene expression actions
of PUFA should be considered among criteria used in defining the
dietary needs of (n-6) and (n-3) and in establishing the dietary ratio
of (n-6) to (n-3) needed for optimum health benefit.
KEY WORDS: • sterol regulatory element binding protein • transcription • fatty acids • diabetes
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