Reduction in hepatic cytochrome P-450 is correlated to the degree of liver fat content in animal models of steatosis in the absence of inflammation.
OBJECTIVE
Fatty liver has been associated with an increased risk of primary graft non-function and drug toxicity. However, these effects have been observed mainly in fatty liver with inflammation, a situation characterized by an overall reduction in cytochrome P-450 (CYP)-dependent activities as well as a contrasting increase in CYP2E1 activity. Our aim was to examine the impact of liver-fat accumulation on CYP in two animal models of fatty liver without necroinflammation.


METHODS
Ducks were force-fed with a high-glucidic diet and male Wistar rats, after 48 h fasting, were refed a high-glucidic, fat-free diet for 48 h. Total CYP, aminopyrine- (AND), erythromycin-N-demethylase (END) and chlorzoxazone hydroxylase (CZOHase) activities as well as CYP2E1 and CYP3A proteins were quantified on microsomal proteins.


RESULTS
Livers from force-fed ducks exhibited significant decreases in total CYP, AND, END and CZOHase activities, inversely correlated with fat-liver content. Refeeding male Wistar rats a high-glucidic, fat-free diet after 48 h fasting, resulting in a 235% increased liver fat content, was associated with a decrease in total CYP (55%), AND (78%), END (55%) and CZOHase (62%) activities as well as in CYP3A (70%) and CYP2E1 (80%) protein content. A significant inverse correlation was observed between CYP and total lipid content.


CONCLUSIONS
In these models of steatosis induced by nutritional manipulations, fat liver accumulation was associated with a significant decrease in CYP activities and in CYP protein expression. Furthermore, the decreases in both CYP content and related activities were correlated with the degree of liver fat content.
Leclercq
I
I
Department of Gastroenterology, Catholic University of Louvain, Brussels, Belgium.
Horsmans
Y
Y
Desager
J P
JP
Delzenne
N
N
Geubel
A P
AP
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D003577:Cytochrome P-450 Enzyme System