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Repression of Pentose Phosphate Pathway Dehydrogenase Synthesis and mRNA by Dietary Fat in Rats^{1 ,2}

Department of Biochemistry, University of California at Riverside, Riverside, CA 92521

We have studied the effects of polyunsaturated fatty acid and its metabolism on the activity, relative synthesis and mRNA levels for rat hepatic glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD). Rats were meal-fed high carbohydrate diets containing either no fat, 5% safflower oil or 5% safflower oil + eicosa-5,8,11,14-tetraynoic acid (TYA). Hepatocytes were isolated and used as a source of RNA, de novo radiolabeled protein and postmitochondrial supernatant for enzyme assay. Dietary safflower oil, as a source of linoleic acid, repressed G6PD activity, synthesis and mRNA levels two- to threefold without significantly changing the amount of carbohydrate consumed. Similar but smaller changes were observed for 6PGD. Dietary fat + TYA (an analogue of arachidonate that inhibits normal metabolism of linoleic acid) prevented the fat-dependent lowering of G6PD and 6PGD activity, synthesis and mRNA levels. Our results suggest that a metabolite of linoleic acid regulates the activity of two lipogenic enzymes, G6PD and 6PGD, by lowering gene expression or mRNA processing or stability.

KEY WORDS: • polyunsaturated fat • glucose-6-phosphate dehydrogenase • 6-phosphogluconate dehydrogenase synthesis • mRNA

¹ Supported in part by the California Agricultural Experiment Station.

² A preliminary report of portions of this work has been published in abstract form [Kim, M., Tomlinson, J. E., Nakayama, R. & Holten, D. (1987) The effect of cAMP, dietary carbohydrate and fat on G6PD synthesis and mRNA levels. Fed. Proc. 46: 2233 (abs.)].

Manuscript received 31 July 1987. Revision accepted 20 November 1987.

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