Biomaterial Database

Cd36 knockout mice are protected against lithogenic diet-induced gallstones. 2017

Yan Xie, and Vincenza Cifarelli, and Terri Pietka, and Elizabeth P Newberry, and Susan M Kennedy, and Amin Khalifeh-Soltani, and Robin Clugston, and Kamran Atabai, and Nada A Abumrad, and Nicholas O Davidson

Gastroenterology Division, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO.

The scavenger receptor and multiligand transporter CD36 functions to promote cellular free fatty acid uptake and regulates aspects of both hepatic and intestinal cholesterol metabolism. However, the role of CD36 in regulating canalicular and biliary cholesterol transport and secretion is unknown. Here, we show that germline Cd36 knockout (KO) mice are protected against lithogenic diet (LD)-induced gallstones compared with congenic (C57BL6/J) controls. Cd36 KO mice crossed into congenic L-Fabp KO mice (DKO mice) demonstrated protection against LD-induced gallstones, reversing the susceptibility phenotype observed in L-Fabp KO mice. DKO mice demonstrated reduced biliary cholesterol secretion and a shift into more hydrophophilic bile acid species, without changes in either BA pool size or fecal excretion. In addition, we found that the mean and maximum force of gallbladder contraction was increased in germline Cd36 KO mice, and gallbladder lipid content was reduced compared with wild-type controls. Finally, whereas germline Cd36 KO mice were protected against LD-induced gallstones, neither liver- nor intestine-specific Cd36 KO mice were protected. Taken together, our findings show that CD36 plays an important role in modifying gallstone susceptibility in mice, at least in part by altering biliary lipid composition, but also by promoting gallbladder contractility.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009119	Muscle Contraction	A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.	Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D002784	Cholesterol	The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.	Epicholesterol
D004032	Diet	Regular course of eating and drinking adopted by a person or animal.	Diets
D005704	Gallbladder	A storage reservoir for BILE secretion. Gallbladder allows the delivery of bile acids at a high concentration and in a controlled manner, via the CYSTIC DUCT to the DUODENUM, for degradation of dietary lipid.	Gallbladders
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001647	Bile Acids and Salts	Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.	Bile Acid,Bile Salt,Bile Salts,Bile Acids,Acid, Bile,Acids, Bile,Salt, Bile,Salts, Bile
D042882	Gallstones	Solid crystalline precipitates in the BILIARY TRACT, usually formed in the GALLBLADDER, resulting in the condition of CHOLELITHIASIS. Gallstones, derived from the BILE, consist mainly of calcium, cholesterol, or bilirubin.	Biliary Calculi,Common Bile Duct Gall Stone,Common Bile Duct Gallstone,Gallstone,Biliary Calculi, Common Bile Duct,Common Bile Duct Calculi,Common Bile Duct Gall Stones,Common Bile Duct Gallstones,Gall Stone,Gall Stones,Gall Stones, Common Bile Duct,Gallstones, Common Bile Duct,Calculi, Biliary