Cd36 knockout mice are protected against lithogenic diet-induced gallstones

Journal of Lipid Research

Nicholas O. Davidson¹  Amin Khalifeh-Soltani²  Kamran Atabai²  Vincenza Cifarelli³  Terri Pietka³  Robin Clugston⁴  Yan Xie⁵  Susan M. Kennedy⁵  Elizabeth P. Newberry⁵  Nada A. Abumrad⁶ 

[1] Department of Medicine, Washington University School of Medicine, St. Louis, MO;Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco, CA;Department of Medicine, Washington University School of Medicine, St. Louis, MO;Department of Physiology, University of Alberta, Edmonton, Canada;Gastroenterology Division, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO;To whom correspondence should be addressed.;

关键词: canalicular cholesterol;    bile acid;    phospholipid;    liver fatty acid binding protein;    gallbladder motility;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown