Regulation of hepatic microsomal cytochrome P450IIE1 level by dietary lipids and carbohydrates in rats.
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.
Yoo
J S
JS
Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers University, Piscataway, NJ 08855-0789.
Ning
S M
SM
Pantuck
C B
CB
Pantuck
E J
EJ
Yang
C S
CS
D000096:Acetone / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology*; D004737:Enflurane / Q000378:metabolism; D008041:Linoleic Acids / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D008041:Linoleic Acids; D000096:Acetone; D003577:Cytochrome P-450 Enzyme System; D004737:Enflurane; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating