Cd36 knockout mice are protected against lithogenic diet-induced gallstones

Abstract

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 knockout (KO) mice are protected against lithogenic diet (LD)-induced gallstones compared with congenic (C57BL6/J) controls. KO mice crossed into congenic KO mice (DKO mice) demonstrated protection against LD-induced gallstones, reversing the susceptibility phenotype observed in 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 KO mice, and gallbladder lipid content was reduced compared with wild-type controls. Finally, whereas germline KO mice were protected against LD-induced gallstones, neither liver- nor intestine-specific 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.

Targeting CD36 as Biomarker for Metastasis Prognostic: How Far from Translation into Clinical Practice?

“…More recent mouse experimental models include double-knockout animals for CD36 and other genes such as leptin [ 51 ], tyrosine-protein kinase Mer [ 52 ], liver-specific signal transducer and activator of transcription (STAT)5 [ 53 ], scavenger receptor-A [ 54 ], scavenger receptor class B type I [ 55 ], heart-specific lipoprotein lipase [ 56 ], apolipoprotein E [ 57 ], and liver-type FA-binding protein [ 58 ].…”

Vitamin D Status of Mice Deficient in Scavenger Receptor Class B Type 1, Cluster Determinant 36 and ATP-Binding Cassette Proteins G5/G8

“…Thus, the overall importance of CD36 for lipid metabolism can be best investigated by use of a global CD36 knockout model, CD36 is assumed to facilitate the cellular uptake of fatty acids [35,36], which may explain the high expression of CD36 in tissues with pronounced fatty acid metabolism, such as adipose tissue and the heart [37]. It appears to be also involved in hepatic cholesterol uptake [38] and biliary cholesterol transport [39]. The increased serum cholesterol and reduced levels of liver cholesterol which we observed in the Cd36 -/mice are consistent with data obtained from Cd36 -/mice [38] and emphasize the impaired hepatic sterol metabolism in these mice.…”

Intestinal CD36 and Other Key Proteins of Lipid Utilization: Role in Absorption and Gut Homeostasis

“…Cd36 − / − mice have been recently reported to be protected from developing gallstones induced by feeding a lithogenic diet (LD) high in cholesterol (167), suggesting a regulatory role of CD36 in canalicular and biliary cholesterol transport and secretion. Hepatic lipid content in LD-fed mice did not identify major differences in total or free cholesterol content, but revealed increased bile acid content in the liver of Cd36 − / − mice.…”

“…Interestingly, CD36 deletion reversed the effect of L-FABP deletion to promote gallstone formation as the double knockout mouse was protected. Neither intestine- nor liver-specific CD36 deletion showed protection against LD induced gallstone formation (167). …”