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Suppression of Rat Hepatic Fatty Acid Synthase and S₁₄ Gene Transcription by Dietary Polyunsaturated Fat¹

Unit of Reproduction and Growth Physiology, The Upjohn Company, Kalamazoo, MI 49001

The objective of this research was to determine whether dietary polyunsaturated fatty acids suppress hepatic fatty acid synthase (FAS) mRNA levels by altering FAS gene transcription. Male Sprague-Dawley rats were meal-fed for 10 d a high glucose diet supplemented with 20% digestible energy as menhaden oil or tripalmitin. The transcription rate for FAS was determined by nuclear run-on analysis in hepatic nuclei isolated from rats 2 h postmeal. The values for transcription rates of FAS and S₁₄ (a putative lipogenic protein) in rats fed menhaden oil were only 6 and 21%, respectively, of the rates in rats fed the tripalmitin diet (p < 0.02). Gene transcription for ß-actin and phosphoenolpyruvate carboxykinase did not differ between treatments. The reduction in hepatic FAS mRNA levels caused by dietary polyunsaturated fats appears to be caused primarily by an inhibition of FAS transcription. The control of transcription by polyunsaturated fats appears not to be mediated by cAMP because the transcription rate for phosphoenolpyruvate carboxykinase (whose gene is very sensitive to cAMP stimulation) was unaffected by the source of dietary fat.

KEY WORDS: • fatty acid synthase • transcription • polyunsaturated fat • gene expression • rat

¹ This work was funded in part by National Institutes of Health grant R01 DK 39302.

² To whom correspondence should be addressed.

Manuscript received 13 March 1990. Revision accepted 14 June 1990.

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