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Polyunsaturated Fatty Acid Regulation of Hepatic Gene Transcription¹

Steven D. Clarke^*,2 and Donald B. Jump

^* Department of Human Ecology, Institute of Molecular Biology, University of Texas-Austin, Austin, Texas 78712-1097 Department of Physiology and Biochemistry, Michigan State University, East Lansing, MI 48824-1101

Polyunsaturated fatty acids (PUFA) modulate the rate of gene transcription for a number of different genes including hepatic lipogenic and glycolytic genes, adipose Glut-4 and stearoyl-CoA desaturase and interleukins. Some of the transcriptional effects of PUFA appear to be mediated by eicosanoids, but the PUFA suppression of lipogenic and glycolytic genes is independent of eicosanoid synthesis and appears to involve a nuclear mechanism directly modified by PUFA. With the recent cloning of a fatty acid-activated nuclear factor termed peroxisome-proliferator-acitivated receptor (PPAR) has come the suggestion that PPAR may be the PUFA response factor. However, this review presents several lines of evidence that indicate that the PPAR and PUFA regulation of gene transcription involves separate and independent mechanisms, and the PPAR is not the PUFA response factor.

KEY WORDS: • polyunsaturated fatty acids • gene transcription

¹ Presented as part of the symposium "Biological Effects of Dietary Arachidonic Acid" given at the Experimental Biology '95 meeting, Atlanta, GA, on April 11, 1995. This symposium was sponsored by the American Institute of Nutrition and was supported by a grant from the Cayman Chemical Company. Guest editors for the symposium were Jay Whelan, University of Tennessee, Knoxville, TN, and J. Bruce German, University of California, Davis, CA.

² To whom correspondence should be addressed: Department of Human Ecology, 115 Gearing, University of Texas-Austin, Austin, TX 78712-1097.

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