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Dietary Polyunsaturated Fats Uniquely Suppress Rat Liver Fatty Acid Synthase and S14 mRNA Content¹

Reproduction and Growth Physiology Research, The Upjohn Company, Kalamazoo, MI 49001 ^* Department of Physiology, Michigan State University, East Lansing, MI 48824

The objective of these studies was to demonstrate that dietary polyunsaturated, but not saturated, fatty acids decrease mRNA abundance for fatty acid synthase (FAS) and S14. A series of experiments involving adult and weanling rats was designed to examine the ability of saturated (tripalmitin), (n-9) monounsaturated (triolein), (n-6) di-unsaturated (safflower oil), and (n-3) polyenic (fish oil) fatty acids to suppress the gene expression of FAS and S14. Dietary polyunsaturated fats reduced by 75–90% the hepatic abundance of FAS and S14 mRNA. Fish oil, rich in 20- and 22-carbon polyenic fatty acids, was more effective than safflower oil, whereas tripalmitin and triolein were without effect. Polyunsaturated fats were also very effective at preventing the rise in FAS and S14 mRNA associated with weaning. The inhibitory action of polyunsaturated fats was rapidly (< 3 h) removed by deleting the fat from the meal. Regression analysis revealed a high correlation (0.81–0.94) between FAS and S14 expression among the various dietary studies. These data support the hypothesis that dietary polyunsaturated fats uniquely regulate the gene expression of lipogenic enzymes and that the mediator is likely a specific entity derived from the long-chain polyenic fatty acids. Moreover, the high correlation between FAS and S14 expression supports the hypothesis that S14 is a member of the lipogenic protein family and has potential as a model gene for the study of FAS expression.

KEY WORDS: • fatty acid synthase • gene expression • fish oil • lipogenesis • rats

¹ This work was supported by National Institutes of Health grants RO1-DK39302 (MKA and SDC) and GM36851 (DBJ).

Manuscript received 24 May 1989. Revision accepted 4 December 1989.

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