Tv. Fungwe et al., STIMULATION OF FATTY-ACID BIOSYNTHESIS BY DIETARY-CHOLESTEROL AND OF CHOLESTEROL-SYNTHESIS BY DIETARY FATTY-ACID, Journal of lipid research, 35(2), 1994, pp. 311-318
We reported previously that dietary cholesterol produces hypertriglyce
ridemia in the rat, accompanied by reduced oxidation and increased inc
orporation of exogenous fatty acid into hepatic triglyceride and incre
ased secretion of very low density lipoprotein. We now report that die
tary cholesterol also increases net hepatic fatty acid synthesis and t
he incorporation of newly synthesized fatty acid into hepatic triglyce
ride in vivo. Male rats were fed a cholesterol-free, semisynthetic die
t (5% [w/w] corn oil) for 7 days, or the same diet supplemented with 0
.5% cholesterol. On the day of the experiments, fed animals received 5
mCi (H2O)-H-3 intraperitoneally (i.p.) either at 1200 h (6 h into the
light cycle) or at 2400 h (6 h into the dark cycle). Animals were kil
led 1 h after receiving the radioisotope. Feeding cholesterol increase
d hepatic triglyceride and cholesteryl ester concentrations, moderatel
y elevated the content of Gee cholesterol, but did not affect phosphol
ipid levels. Increased net synthesis of fatty acids by livers of anima
ls receiving cholesterol was observed during the dark period; a simila
r increase during the light period was also observed for incorporation
of newly synthesized fatty acid into hepatic phospholipid and cholest
eryl ester, although incorporation into triglyceride was of borderline
significance (P < 0.06). In other experiments male rats were fed simi
lar diets for 3, 7, or 21 days. Fed animals received 10 mCi (H2O)-H-3,
i.p. (900-1000 h), and were killed 24 h later. Duration of feeding di
d not influence rates of net fatty acid synthesis or the stimulation b
y cholesterol of incorporation of newly synthesized fatty acid into he
patic triglyceride and cholesteryl ester. Increasing the fat content o
f the diet to 20% (w/w) and maintaining the cholesterol supplement at
0.5% diminished the net rate of hepatic lipogenesis, but the stimulato
ry effect of cholesterol was still evident. Biosynthesis of cholestero
l was stimulated when the fat content of the diet was increased in the
absence or in the presence of added cholesterol. These data indicate
that dietary cholesterol stimulates the biosynthesis of fatty acids, w
hile the addition of triglyceride to the diet stimulates synthesis of
cholesterol. Fatty acid and cholesterol appear to stimulate each other
's biosynthesisin the liver.