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 (etomo xir) and (R)-3-carboxy-N,N,N-trimethyl-2-{[hydroxy(tetradecyloxy)phosphinyl ]oxy}-1-propanaminium hydroxide (SDZ CPI 975), on cardiac and hepatic hyper trophy in ddY mice. One-week administration of etomoxir caused cardiac and hepatic hypertrophy, 19% and 22% as a ratio to body weight, respectively. A lthough 4-week administration of etomoxir caused hepatic hypertrophy, there was no significant change in liver triglyceride content in the first or se cond week. In cultured HepG(2) cells, etomoxir treatment (1 week) did not c ause triglyceride to accumulate. One-week administration of SDZ CPI 975 cau sed neither cardiac nor hepatic hypertrophy. In vitro, neither drug had sel ectivity for carnitine palmitoyltransferase I isozymes. These findings sugg est that the hepatic hypertrophy following 1- or 2-week treatment with etom oxir is caused by mechanisms different from those responsible for triglycer ide accumulation, and that inhibition of carnitine palmitoyltransferase I m ay not necessarily induce hepatic hypertrophy. (C) 2000 Elsevier Science B. V. All rights reserved.