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Nutritional Control of Rat Liver Fatty Acid Synthase and S14 mRNA Abundance¹

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

The objective of this research was to evaluate the change in abundance of S14 and fatty acid synthase (FAS) mRNAs under a variety of nutritional conditions to evaluate the hypothesis that the regulation of the S14 gene is similar to that of other proteins involved in lipid metabolism and that changes in S14 expression are comparable to those that occur in FAS expression. Livers from rats fed a high carbohydrate diet were found to contain 350- and 100-fold more S14 and FAS mRNA than livers from rats fasted for 48 h. Although feeding a high fat diet increased S14 and FAS mRNA above fasting (P < 0.05), the level of S14 and FAS mRNAs was only 5% and 4%, respectively, of the amount in the high carbohydrate group. Both S14 and FAS mRNAs accumulated quickly upon intubation of fasted rats with a solution of sucrose. The earliest rise in these mRNAs occurred within 60 min; by 240 min after gavage, each mRNA had increased 30-fold. The rapid induction of FAS and S14 mRNAs was also observed during ingestion of a high glucose meal. Hepatic FAS and S14 mRNA decreased 80–90% and 60%, respectively, during the 21-h interval between meals. This degree of mRNA loss was estimated to require a half-life for FAS and S14 mRNA of < 8 h and < 12 h, respectively. Regression analysis of the three dietary studies revealed a correlation coefficient for the relationship between S14 and FAS mRNA abundance ranging between 0.88 and 0.96. Such a high correlation coefficient supports the hypothesis that the S14 gene may have potential as a model for study of expression of proteins involved in lipid metabolism.

KEY WORDS: • fatty acid synthase • gene expression • lipogenesis • mRNA abundance • rats

¹ Supported by National Institutes of Health grants RO1 DK 39302 (SDC, MKA) and GM 36851 (DBJ).

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

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