The mechanism of increased gallstone formation in obese human subjects

Cholesterol gallstones occur three times more frequently in morbidly obese subjects than in normal controls. The present study tests the hypothesis that 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 eight 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 hour periods on consecutive days. Gallbladder bile of seven of eight subjects was saturated consistently with cholesterol. Mean hourly hepatic cholesterol excretion in bile was 0.232 mM. per hour, three 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. per 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 (X = 2.72 Gm.) but the daily synthesis of bile acids was increased (X = 0.86 Gm. of cholic acid). We conclude that the clinically observed high correlation of cholelithiasis with obesity is due to increased hepatic secretion of cholesterol which precipitates as cholesterol gallstones.