Stimulation of cholesterol and lipid synthesis by insulin in familial hypercholesterolemic fibroblasts

Cultured skin fibroblasts from two patients with homozygous familial hypercholesterolemia and three normal subjects were preincubated for 24 hours in medium containing 10% delipidated serum with insulin concentrations of 0.4, 4, or 40 ng/mL. [14C]acetate incorporation into total lipids, cholesterol, and phospholipids was significantly increased in familial hypercholesterolemic cells at insulin concentrations of 0.4 and 4 ng/mL, which had no effect in normal cells. When the data were normalized as percent stimulation over control for individual experiments, [14C]acetate incorporation into cholesterol was comparable at 40 ng/mL in both cell types. Similar results were obtained in cells preincubated in serum free artificial medium. Coordinate increases in the activity of 3-hydroxy-3-methylglutaryl CoA reductase in response to insulin were not found. These studies show that familial hypercholesterolemic cells have an altered lipogenic response to low concentrations of insulin.