Hepatic esterification rate of cholesterol and biliary lipids in human obesity

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)