CARNITINE PALMITOYLTRANSFERASE MODULATION OF HEPATIC FATTY-ACID METABOLISM AND RADIO-HPLC EVIDENCE FOR LOW KETOGENESIS IN NEONATAL PIGS

A neonatal piglet model was used to study hepatic fatty acid metabolis m during the early postnatal period, Hepatocytes were isolated from pi gs at birth or after 24 h, in fed or unfed states (n = 4 pigs/group). Cells were incubated with 1 mmol/L [1-C-14]-octanoate (C8) or -palmita te (C16) in the presence or absence of 1 mmol/L L-carnitine, carnitine plus tetradecylglycidic acid (TDGA; 10 mu mol/L) or carnitine plus gl ucagon (0.5 mu g/L). Accumulation of radiolabel [nmol/(h . 10(6) cells )] in CO2 and acid-soluble products (ASP) was higher (3.5- and 4.5-fol d, respectively) from C8 than from C16 (P < 0.0001), Glucagon, carniti ne and TDGA had no effect on the oxidation of C8 (P > 0.1). Carnitine addition tended to increase C16 flux to ASP [from 5.3 to 7.6 nmol/(h . 10(6) cells); P < 0.1], whereas carnitine plus TDGA decreased flux (f rom 7.6 to 2.1; P < 0.001), Esterified products accounted for 70% of m etabolized label in control C16 incubations; this was reduced to 62% b y carnitine (P < 0.05) and increased to 80% by the addition of carniti ne plus TDGA (P < 0.0001), The 1-C-14 flux to CO2 in cells from 24-h-o ld unfed piglets was 47% lower than from fed pigs (P < 0.01) but 28% h igher than in pigs at birth, Radiolabel contained in ASP and total met abolized label were 48% lower from unfed pigs compared with the piglet s at birth and 24-h-old fed pigs (P < 0.01) and were paralleled by cha nges in oxygen consumption, Radio-HPLC analysis of ASP revealed minima l radiolabel accumulation in ketone bodies. Up to 40% of radioactivity in ASP was presumptively identified as acetate, These data illustrate that hepatic C16 metabolism in piglets can be altered by changes in t he activity of carnitine palmitoyltransferase I during the neonatal pe riod and that ketone bodies do not represent a major route of hepatic fatty acid carbon flux.