MECHANISM OF INCREASED GALLSTONE FORMATION IN OBESE HUMAN SUBJECTS

Abstract

Cholesterol gallstones occur 3 times more frequently in morbidly obese subjects than in normal controls. Obese subjects develop gallstones because of relative and absolute excess cholesterol excretion in bile. The steady-state kinetics of biliary lipid excretion and bile acid pool sizes were determined in 8 healthy obese subjects without gallstones by a noninvasive technique. Aliquots of resting gallbladder bile were obtained on consecutive days. Hepatic bile excretion was constantly sampled during the infusion of a liquid isocaloric cholesterol-free formula containing a dilution indicator over two 12 h periods on consecutive days. Gallbladder bile of 7 of 8 subjects was saturated consistently with cholesterol. Mean hourly hepatic cholesterol excretion in bile was 0.232 mM/hour, 3 times greater than that of normal subjects and twice that of subjects with gallstones. Phospholipid and bile acid excretion were 0.73 and 1.88 mM/hour, respectively. The excretion rates of these cholesterol-solubilizing components of bile are higher than in normal subjects but are insufficient to compensate for the increased cholesterol excretion. The bile acid pool sizes were normal (SB + X = 2.72 Gm.) but the daily synthesis of bile acids was increased (SB + X = 0.86 Gm. of cholic acid). The clinically observed high correlation of cholelithiasis with obesity is due to increased hepatic secretion of cholesterol which precipitates as cholesterol gallstones.