STIMULATION OF FATTY-ACID BIOSYNTHESIS BY DIETARY-CHOLESTEROL AND OF CHOLESTEROL-SYNTHESIS BY DIETARY FATTY-ACID

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.