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Regulation of Hepatic Microsomal Cytochrome P450IIE1 Level by Dietary Lipids and Carbohydrates in Rats¹

Jeong-Sook H. Yoo^*,2, Shu M. Ning^*, Carol B. Pantuck^*,, Eugene J. Pantuck^*, and Chung S. Yang^*

^* Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers University, Piscataway, NJ 08855-0789 Department of Anesthesiology, Columbia College of Physicians and Surgeons, New York, NY 10032

The present work tests the hypothesis that high fat/low carbohydrate diets elevate the level of liver microsomal cytochrome P450IIE1. Male Sprague-Dawley rats were fed liquid diets containing varied ratios of corn oil/carbohydrate for 4 d. Rats fed diets with higher fat/carbohydrate ratios produced higher serum acetone levels and higher hepatic microsomal P450IIE1 content and N-nitrosodimethylamine demethylase activity than those fed diets with lower fat/carbohydrate ratios. This dietary fat/carbohydrate effect on P450IIE1 also was observed with modified semipurified AIN-76A diets. In addition, both the quantity and the extent of unsaturation of dietary lipids affected P450IIE1 regulation. At moderate fat levels (5 and 20% diet), rats fed corn oil and menhaden oil diets produced higher P450IIE1 activity than those fed lard and olive oil diets. Rats fed a diet containing 20% corn oil or an amount of linoleic acid equivalent to the 20% corn oil diet showed twofold to threefold increases in the level of P450IIE1 over those fed a fat-free diet. Rats fed a 25% corn oil diet showed twofold higher enflurane metabolism in vivo than those fed a 0.5% corn oil diet. The present results suggest that the constitutive P450 enzyme level is regulated by dietary fat/carbohydrate ratios.

KEY WORDS: • lipids • linoleic acid • cytochromes P450 • rats • liver

¹ The present work was supported by National Institutes of Health grants GM 38336, ES 03938 and ES 05022 and was presented in part at the Annual Meeting of the Federation of American Societies for Experimental Biology, Las Vegas, NV, May, 1988 [Yoo, J.-S.H., Park, H. S. & Yang, C. S. (1988) The effect of ketogenic and glucogenic diets on the induction of P-450ac. FASEB J. 2: A1633 (abs. 7759)].

² To whom correspondence should be addressed.

Manuscript received 9 July 1990. Revision accepted 12 December 1990.

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