Mechanisms of Lithogenic Bile Formation in American Indian Women with Cholesterol Gallstones

Abstract

A B S T R A C T Hepatic secretions of biliary lipids were estimated in 43 patients with and without cholesterol gallstones. Studies were carried out by a marker dilution technique employing duodenal intubation with a threelumen tube. Hourly secretion rates of cholesterol, bile acids, and phospholipids were determined during constant infusion with liquid formula.In 17 American Indian women with gallstones, hourly outputs of biliary bile acids were significantly less than those in 7 Indian men and 12 Caucasian women without gallstones. These findings suggest that a decreased hepatic secretion of bile acids contributes significantly to the production of a lithogenic bile in Indian women. However, in Indian women witlh gallstones, secretion of biliary cholesterol was also significantly increased, as compared with Caucasian women without stones. Therefore, lithogenic bile in Indian women was, in most cases. due to a combined decrease in bile acid output and increase in cholesterol secretion.In an attempt to determine the mechanisms for these abnormalities, cholesterol balance studies were done in Indian women with gallstones and normal Indian men. Balance data were compared with results reported previously in non-Indian patients studied by the same techniques, and in general, Indian women showed a slight increase in fecal excretion of bile acids. Since bile acids in the enterohepatic circulation were

Biliary lipid secretion in man

“…[41] that cholesterol secretion in obese gallstone subjects is greater than in obese non-gallstone subjects seems, however, to suggest that a metabolic defect may be present in the former group of subjects superimposed on the well-known cholesterol hypersecretion of obesity. Combined solvent deficiency and solute excess has also been reported by Grundy et al [99] in American Indian women with cholesterol gallstones. In this study also most of the patients were obese, and this condition may act as an additional cause of excess cholesterol secretion.…”

Gallstones associated with nonalcoholic steatohepatitis (NASH) and metabolic syndrome

“…Obesity is a well-established risk factor for NASH and a major risk factor for developing gallstones (7).The risk for gallbladder stones is especially high if obesity onsets in yo- uth. Gallbladder stones are closely related to central obesity, diabetes mellitus and insulin resistance (8,9). Other shared risk factors include dyslipidemia (hypertriglyceridemia, low HDL-C) and abnormalities in fibrinolysis and coagulation (10).…”

Modulation of intrahepatic cholesterol trafficking: evidence by in vivo antisense treatment for the involvement of sterol carrier protein-2 in newly synthesized cholesterol transport into rat bile

“…Our results give rise to the possibility that regulation of liver SCP-2 activity may influence both the intrahepatic cholesterol compartmentalization and sterol balance in the whole animal. Finally, it could be possible that some high biliary cholesterol secretory states, such as those associated with obesity and gallstone disease [3,58], could be mediated by liver SCP-2 overexpression. …”