CAR Activation Averts Cholesterol Gallstone Formation in Mice

MONDAY, March 20, 2017 (HealthDay News) — Constitutive androstane receptor (CAR) activation decreases the biliary cholesterol concentration and can prevent formation of cholesterol gallstone disease (CGD), according to an experimental study published online March 7 in The American Journal of Pathology.

In an effort to study the dynamics of biliary lipids, Shihai Cheng, from Sichuan University in Chengdu, China, and colleagues treated C57BL6/J mice maintained on a lithogenic diet with CAR agonist 1,4-bis-[2-(3, 5-dichlorpyridyloxy)] benzene and performed bile duct cannulation.

The researchers found that CAR activation reduced the biliary cholesterol concentration and prevented formation of CGD. The lower biliary cholesterol concentration was mainly due to suppression of Abcg5 and Abcg8 expression in CAR-activated mice. CAR activation also increased expression of Cyp7a1, promoting cholesterol conversion into bile acids. CAR activation enhanced reabsorption of bile acid by increasing bile acid transporters Asbt and Ostβ expression in the ileum. There was also improvement of hepatic steatosis in the liver of CAR-activated mice. Activation of CAR provided protection against the liver X receptor-α-sensitized CGD by suppression of Abcg5/8 expression.

“Collectively, CAR plays an important role in maintaining the homeostasis of cholesterol, bile acids, and triglycerides levels, and it might be a promising therapeutic target for preventing or treating CGD,” the authors write.

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