Fate of intravenously administered squalene in the rat

To investigate the metabolism of serum squalene rats were given intravenously serum or isolated lipoprotein containing [3H]squalene and [14C]cholesterol. Labeled squalene disappeared multiexponentially from serum and the rate of disappearance was consistently faster than for [14C]cholesterol. [3H]Squalene given by injection did not accumulate in tissues, but was rapidly cyclized to sterols, resulting in the labeling of serum methyl sterols and cholesterol as well as biliary and fecal sterols and bile acids. Independent of the form of administration, the fractional conversion of squalene to serum cholesterol was less than one. This was caused by the fact that [3H]squalene was eliminated initially more rapidly than serum [14C]cholesterol in the feces and was converted to a greater extent than serum cholesterol to bile acids, whereas both labels were eliminated in parallel as neutral sterols. The results support the role of newly synthesized hepatic cholesterol as the preferred substrate of bile acid synthesis.