Obesity is often associated with an increased hepatic secretion rate of
cholesterol and saturated gallbladder bile. In order to evaluate the role of hepatic esterification of
cholesterol in this phenomenon, we assayed the activity of
acyl CoA:
cholesterol acyl
transferase (ACAT), which catalyzes the esterification of
cholesterol, in liver microsomes obtained from 19 morbidly obese patients without
gallstones undergoing
vertical banded gastroplasty. Gallbladder bile was obtained and analyzed for
lipid composition,
cholesterol saturation, nucleation time, and occurrence of
cholesterol crystals. Fourteen non-obese
gallstone-free subjects undergoing
cholecystectomy because of suspected
polyp or
adenomyoma in the gallbladder served as controls. The hepatic content of esterified
cholesterol was increased by about 70% in the obese patients (P < 0.05). Still, the mean levels of the ACAT activity were equal in the obese and non-obese patient groups (11 +/- 1 and 11 +/- 2 pmol/min per mg
protein, respectively). When exogenous
cholesterol was added to the assay system, the activity was increased markedly in both groups. The ACAT activity was higher in obese patients with steatosis of the liver compared with those displaying normal liver morphology (12 +/- 1 vs 8 +/- 1 pmol/min per mg, P < 0.05). Obese patients did not have significantly more saturated gallbladder bile than the non-obese controls (84 +/- 7 and 77 +/- 8%, respectively). They had a normal nucleation time and their gallbladder bile did not contain any
cholesterol crystals. We conclude that obese patients without
gallstones usually have a normal esterification rate of
cholesterol in the liver. Steatosis of the liver was associated with increased ACAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)