HEPATIC ESTERIFICATION RATE OF CHOLESTEROL AND BILIARY LIPIDS IN HUMAN OBESITY

Obesity is often associated with an increased hepatic secretion rate o f 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 undergoin g vertical banded gastroplasty. Gallbladder bile was obtained and anal yzed for lipid composition, cholesterol saturation, nucleation time, a nd occurrence of cholesterol crystals. Fourteen non-obese gallstone-fr ee subjects undergoing cholecystectomy because of suspected polyp or a denomyoma in the gallbladder served as controls. The hepatic content o f esterified cholesterol was increased by about 70% in the obese patie nts (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 add ed to the assay system, the activity was increased markedly in both gr oups. 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 ha ve significantly more saturated gallbladder bile than the non-obese co ntrols (84 +/- 7 and 77 +/- 8%, respectively). They had a normal nucle ation time and their gallbladder bile did not contain any cholesterol crystals. We conclude that obese patients without gallstones usually h ave a normal esterification rate of cholesterol in the liver. Steatosi s of the liver was associated with increased ACAT activity. Only few o f the obese patients had saturated gallbladder bile. There was no corr elation between saturation of bile and ACAT activity, indicating that the rate of esterification of cholesterol in the liver is of little re gulatory importance for the cholesterol saturation of bile in humans w ithout gallstones.