Abstract
Cholesterol gallstones occur rarely in childhood and adolescence and increase linearly with age in both genders. To explore whether aging per se increases cholesterol saturation of bile and gallstone prevalence, and to investigate age-related changes in hepatic and biliary lipid metabolism, we studied gallstone-susceptible C57L mice and resistant AKR mice of both genders fed 8 weeks with a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butter fat starting at (young adult) 8, (older adult) 36, and (aged) 50-weeks-of-age. After the 8-week feeding, gallstone prevalence, gallbladder size, biliary lipid secretion rate, and HMG-CoA reductase activity were significantly greater but cholesterol 7alpha-hydroxylase activity was lower in C57L mice of both genders compared with AKR mice. Increasing age augmented biliary secretion and intestinal absorption of cholesterol, reduced hepatic synthesis and biliary secretion of bile salts, and decreased gallbladder contractility, all of which increased susceptibility to cholesterol cholelithiasis in C57L mice. We conclude that aging per se is an independent risk factor for cholesterol gallstone formation. Because aging increases significantly biliary cholesterol hypersecretion and gallstone prevalence in C57L mice carrying Lith genes, it is highly like that Longevity (aging) genes can enhance lithogenesis of Lith (gallstone) genes.
Highlights
Cholesterol gallstones occur rarely in childhood and adolescence and increase linearly with age in both genders
In this study, using a unique genetically gallstone-susceptible C57L mouse model with Lith genes [2, 3, 29] compared to resistant AKR mice, we investigated age-related hepatic cholesterol and bile salt metabolism, biliary lipid secretion rate, gallbladder bile lipid composition, gallbladder motility function, and intestinal cholesterol absorption, as well as gallstone prevalence rate
Our results showed that aging per se increases cholesterol gallstone formation through enhancing biliary secretion and intestinal absorption of cholesterol, decreasing hepatic synthesis and secretion of bile salts, and reducing gallbladder contractility in C57L mice
Summary
Cholesterol gallstones occur rarely in childhood and adolescence and increase linearly with age in both genders. To explore whether aging per se increases cholesterol saturation of bile and gallstone prevalence, and to investigate age-related changes in hepatic and biliary lipid metabolism, we studied gallstone-susceptible C57L mice and resistant AKR mice of both genders fed 8 weeks with a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butter fat starting at (young adult) 8, (older adult) 36, and (aged) 50-weeks-of-age. In this study, using a unique genetically gallstone-susceptible C57L mouse model with Lith genes [2, 3, 29] compared to resistant AKR mice, we investigated age-related hepatic cholesterol and bile salt metabolism, biliary lipid secretion rate, gallbladder bile lipid composition, gallbladder motility function, and intestinal cholesterol absorption, as well as gallstone prevalence rate. Our results showed that aging per se increases cholesterol gallstone formation through enhancing biliary secretion and intestinal absorption of cholesterol, decreasing hepatic synthesis and secretion of bile salts, and reducing gallbladder contractility in C57L mice
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