J. Odle et al., CARNITINE PALMITOYLTRANSFERASE MODULATION OF HEPATIC FATTY-ACID METABOLISM AND RADIO-HPLC EVIDENCE FOR LOW KETOGENESIS IN NEONATAL PIGS, The Journal of nutrition, 125(10), 1995, pp. 2541-2549
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.