Stimulation of fatty acid biosynthesis by dietary cholesterol and of cholesterol synthesis by dietary fatty acid

We reported previously that dietary cholesterol produces hypertriglyceridemia in the rat, accompanied by reduced oxidation and increased incorporation of exogenous fatty acid into hepatic triglyceride and increased secretion of very low density lipoprotein. We now report that dietary cholesterol also increases net hepatic fatty acid synthesis and the incorporation of newly synthesized fatty acid into hepatic triglyceride in vivo. Male rats were fed a cholesterol-free, semi- synthetic diet (5% (wlw) corn oil) for 7 days, or the same diet supplemented with 0.5% cholesterol. On the day of the experi- ments, fed animals received 5 mCi 3H20 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 killed 1 h after receiving the radi- oisotope. Feeding cholesterol increased hepatic triglyceride and cholesteryl ester concentrations, moderately elevated the content of free cholesterol, but did not affect phospholipid levels. In- creased net synthesis of fatty acids by livers of animals receiving cholesterol was observed during the dark period; a similar in- crease during the light period was also observed for incorpora- tion of newly synthesized fatty acid into hepatic phospholipid and cholesteryl ester, although incorporation into triglyceride was of borderline significance (P < 0.06). In other experiments male rats were fed similar diets for 3, 7, or 21 days. Fed animals received 10 mCi 3H20, i.p. (900-1000 h), and were killed 24 h later. Duration of feeding did not influence rates of net fatty acid synthesis or the stimulation by cholesterol of incorporation of newly synthesized fatty acid into hepatic triglyceride and cholesteryl ester. Increasing the fat content of the diet to 20% (w/w) and maintaining the cholesterol supplement at 0.5% diminished the net rate of hepatic lipogenesis, but the stimula- tory effect of cholesterol was still evident. Biosynthesis of cholesterol was stimulated when the fat content of the diet was increased in the absence or in the presence of added cholesterol. I These data indicate that dietary cholesterol stimulates the biosynthesis of fatty acids, while the addition of triglyceride to the diet stimulates synthesis of cholesterol. Fatty acid and cholesterol appear to stimulate each other's biosynthesis in the liver.-Fungwe, T. V., J. E. Fox, L. M. Cagen, H. G. Wilcox, and M. Heimberg. Stimulation of fatty acid biosynthe- sis by dietary cholesterol and of cholesterol synthesis by dietary fatty acid. J Lipid Res. 1994. 35: 311-318.