Cholesterol precursors and their diurnal rhythm in lipoproteins of patients with jejuno-ileal bypass and ileal dysfunction

Abstract

Cholesterol synthesis and its diurnal variation was studied by measuring squalene, free and esterified methyl sterols and cholesterol, and triglycerides in serum lipoproteins every four hours over a period of 24 hours in controls and in patients with jejunoileal bypass or ileal exclusion. Fat absorption, as indicated by postprandial increase of very-low-density lipoprotein (VLDL) lipids (including chylomicrons) and fecal fat, was markedly impaired in jejunoileal bypass. Fecal analysis indicated that bile acid malabsorption enhanced cholesterol synthesis about sixfold in ileal dysfunction, and twofold in jejunoileal bypass with moderate bile acid and cholesterol malabsorption. The squalene contents were not increased consistently in the VLDL and combined low-density plus high-density lipoproteins (LDL + HDL) of the two operated groups and, in contrast to the controls, the diurnal variation was inconsistent. The levels of unesterified methyl sterols, delta 8-dimethylsterol and delta 8-methostenol in particular, were several times higher throughout the 24 hour period in the lipoproteins of the two patient groups than of the controls, were higher in ileal dysfunction than jejunoileal bypass, exhibited a constant diurnal rhythm in the controls but only in the relatively small VLDL fraction (not in the large LDL + HDL) of the operated groups, and were positively correlated with cholesterol synthesis in the three groups combined (for methyl sterols in VLDL r = 0.740 and in LDL + HDL r = 0.869). Esterified methyl sterols were also increased in the operated groups but were not correlated with cholesterol synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)