Sterol synthesis from biliary squalene in the jejunal mucosa of the rat in vivo

Abstract

Because bile contains substantial amounts of cholesterol precursors, e.g., squalene and differnet methyl sterols, the fate of biliary squalene was studied by incubating isolated jejunal loops of the rat in vivo with bile containing³H-squalene and¹⁴C-cholesterol. After 90 min, no radioactivity was found in plasma lipids. Closer analysis of gut epithelium revealed that both labeled compounds were preferentially taken up by the villous cells. Biliary³H-squalene was absorbed almost completely and was further cyclized to free and esterified methyl sterols and cholesterol. Whereas squalene not cyclized to sterols stayed in the mucosa, the newly synthesized sterols were transferred to lumen. The lipid patterns of gut lumen and mucosal cells were quite different, suggesting that the transfer of the newly synthesized lipid to intestinal lumen was not due to the desquamation of epithelial cells alone. The results suggest that biliary cholesterol precursors can contribute to the cholesterol production of the jejunal villous cells bypassing the rate-limiting step of the cholesterol synthesis pathway, and to the “nonexchanging” fecal neutral sterols of the rat.