Role of acetone, dietary fat and total energy intake in induction of hepatic microsomal ethanol oxidizing system.
Chronic ethanol consumption results in the induction of a specific hepatic cytochrome P-450 (P450IIE1). However, since compounds other than ethanol (i.e., acetone) can also serve as P450IIE1 inducers, and since ethanol given with a normal fat-containing (35% of energy) diet is associated with acetonemia, hepatic steatosis and decreased body weight gain, the question has been raised whether induction is mediated specifically by ethanol or whether it might represent a nonspecific response to these other factors. This was investigated by varying both the mode of ethanol administration and the composition of the diet. By administering ethanol in the drinking water, or as part of a low-fat (5% of energy) liquid diet, a significant induction of P450IIE1 and of the activities of the microsomal ethanol oxidizing system and p-nitrophenol hydroxylase was demonstrated in the absence of any significant increase in blood acetone with minimal increase in liver total lipids. Induction of P450IIE1 was comparable with the low or normal fat-containing diets, but MEOS activity rose more with the latter, possibly reflecting a potentiating effect of dietary fat on ethanol oxidation by P-450 enzymes other than P450IIE1. When the lack of weight gain of the alcohol fed animals was mimicked in controls by decreasing the amount of diet ingested, no induction was observed. Varying the pattern of liquid diet feeding had no demonstrable differential effect. Thus, the induction of P450IIE1 after chronic ethanol consumption can be attributed to ethanol itself, but dietary fat can potentiate the induction of the microsomal ethanol oxidizing system and of p-nitrophenol hydroxylase.
Lieber
C S
CS
Section of Liver Disease and Nutrition, Bronx Veterans Administration Medical Center, New York.
Lasker
J M
JM
DeCarli
L M
LM
Saeli
J
J
Wojtowicz
T
T
D000096:Acetone / Q000494:pharmacology*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004041:Dietary Fats / Q000494:pharmacology*; D002149:Energy Intake; D004790:Enzyme Induction; D000431:Ethanol / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D004041:Dietary Fats; D007527:Isoenzymes; D000096:Acetone; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System