Effects of weight reduction on squalene, methyl sterols and cholesterol and on their synthesis in human adipose tissue.

Quantitation of cholesterol and its precursors from human adipose tissue biopsies revealed very high squalene and moderately high methyl sterol concentrations. The squalene and cholesterol values were correlated with each other. Weight reduction in obese subjects following a jejuno-ileal bypass resulted in a significant but transient increase in adipose tissue cholesterol. The squalene concentration was also increased postoperatively, the maximum being reached about 6 months later than that of cholesterol as if the mobilization of squalene from shrunken adipocytes had been slow. Weight reduction with a 2--14 day total fast significantly reduced the adipocyte size but had no consistent effect on adipose tissue squalene, methyl sterol and cholesterol concentrations or on their adipocyte contents. Incubation of adipose tissue with labelled acetate and mevalonate revealed that the bulk of the labels in non-saponifiable lipids stayed in the large intermediate pools of methyl sterols and squalene in particular, fairly little being found in the cholesterol fraction itself. The total fast inhibited the incorporation of both 14C-acetate and 3H-mevalonate to squalene, methyl sterols and cholesterol, suggesting that cholesterol synthesis was inhibited before and after the mevalonate step.