Modulation of cytochrome P450 enzymes in response to continuous or intermittent high-fat diet in pigs.
1. To date, no information has been available on the modulation of cytochrome P450 enzymes (CYPs) following the administration of a hyperlipidemic diet in pigs. 2. We investigated the potential modulation of xenobiotic-metabolizing CYPs in liver, heart and duodenum of pigs subjected to a high-fat/high-cholesterol diet for 2 months continuously (C-HFD) or on alternate weeks (A-HFD). 3. The administration of the high-fat diet resulted in considerably increased plasma cholesterol levels although the animals were still able to manage the lipid overload efficiently, and no sign of effective tissue inflammation occurred in livers. Plasma lipid profile and liver histology indicated a better adaptive response of the A-HFD pigs compared to the C-HFD group. We showed a post-transcriptional induction of hepatic CYP2E1 activity in C-HFD pigs and a transcriptional induction of hepatic CYP3As - especially in the A-HFD group. No further CYP modulation was observed in either liver or extra-hepatic tissues. 4. In conclusion, the administration of a high-fat diet in pigs resulted in limited effects on the drug metabolism system. The better adaptive response of A-HFD pigs compared to C-HFD pigs is a very interesting observation since the intermittent administration of the diet reflects the mode of human behavior more closely.
Institute of Clinical Physiology - IFC, Pisa, Italy. e.puccinelli@gmail.co
Emanuela
E
Puccinelli
Pier Giovanni
PG
Gervasi
Gualtiero
G
Pelosi
Mariarita
M
Puntoni
Vincenzo
V
Longo
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D008055:Lipids / Q000097:blood; D008099:Liver / Q000166:cytology / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D060888:Real-Time Polymerase Chain Reaction; D034421:Sus scrofa; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D003577:Cytochrome P-450 Enzyme System