Effects of carnitine palmitoyltransferase I inhibitors on hepatic hypertrophy.
We investigated the effect of two types of carnitine palmitoyltransferase I inhibitors, ethyl 2-(6-(4-chlorophenoxy)hexyl)oxirane-2-carboxylate (etomoxir) and (R)-3-carboxy-N,N, N-trimethyl-2-¿[hydroxy(tetradecyloxy)phosphinyl]oxy¿-1-propana minium hydroxide (SDZ CPI 975), on cardiac and hepatic hypertrophy in ddY mice. One-week administration of etomoxir caused cardiac and hepatic hypertrophy, 19% and 22% as a ratio to body weight, respectively. Although 4-week administration of etomoxir caused hepatic hypertrophy, there was no significant change in liver triglyceride content in the first or second week. In cultured HepG(2) cells, etomoxir treatment (1 week) did not cause triglyceride to accumulate. One-week administration of SDZ CPI 975 caused neither cardiac nor hepatic hypertrophy. In vitro, neither drug had selectivity for carnitine palmitoyltransferase I isozymes. These findings suggest that the hepatic hypertrophy following 1- or 2-week treatment with etomoxir is caused by mechanisms different from those responsible for triglyceride accumulation, and that inhibition of carnitine palmitoyltransferase I may not necessarily induce hepatic hypertrophy.
Yotsumoto
T
T
Shiraoka Research Station of Biological Science, Nissan Chemical Industries Ltd., 1470, Shiraoka, Minamisaitama, Saitama, 349-0294, Japan.
Naitoh
T
T
Kitahara
M
M
Tsuruzoe
N
N
D000214:Acyl Coenzyme A / Q000494:pharmacology; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006801:Humans; D006984:Hypertrophy / Q000139:chemically induced; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D063065:Organophosphonates / Q000494:pharmacology; D013997:Time Factors; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000214:Acyl Coenzyme A; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D005227:Fatty Acids; D063065:Organophosphonates; D014280:Triglycerides; C077864:etomoxiryl-coenzyme A; D002334:Carnitine O-Palmitoyltransferase; C110822:SDZ CPI 975; C054207:etomoxir