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SUMMARY Cholesterol synthesis, faecal bile acids and neutral sterols, and plasma squalene and free and esterified cholesterol precursor sterols concentrations were studied in patients with previous ileal resection (n=30) or jejunoileal bypass (n=9) to elucidate the responses of different cholesterol precursors to enhanced cholesterol synthesis induced by cholesterol and bile acid malabsorption. A subgroup of seven resection patients without fat and bile acid malabsorption served as controls. Of the resection patients, eight had a pure bile acid malabsorption and 15 a combination of fat, bile acid, and modest cholesterol malabsorption. In the patients with jejunoileal bypass, cholesterol and fat absorption was greatly decreased in addition to bile acid malabsorption. The overall cholesterol synthesis was associated with proportionately increased plasma contents of free (and, less consistently, esterified) methyl sterols, the most marked increase, up to 18 times, being recorded for free and esterified lathosterols. The concentrations of the precursor sterols were similarly increased in the subjects with bile acid and cholesterol malabsorption, the two lathosterols showing the highest correlations with the overall cholesterol synthesis (r=0.820-0941). In the subjects with jejunoileal bypass cholesterol malabsorption effectively regulated cholesterol synthesis and the precursor levels. Gut exclusions large enough to cause cholesterol and/or bile acid malabsorption activate cholesterol synthesis leading to a proportional elevation in the plasma concentrations of cholesterol precursors, especially in those of lathosterols and free methyl sterols. Determination of the plasma concentration of total lathosterol by a single gas-chromatographic run is a suitable method for rapid screening of clinically significant cholesterol and bile acid malabsorption.

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Clofibrate treatment decreased drastically the activity of serum postheparin lipoprotein lipase of rats fed with fat-free test diet but had no effect on hepatic lipase. 3 weeks’ treatment was followed by a significant fall in serum cholesterol caused by a marked decrease in HDL-cholesterol. Clofibrate decreased in vitro synthesis of cholesterol and fatty acids in jejunal villous cells but not in the crypt cells.

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