Ample dietary fat reduced the risk of primary vesical calculi by inducing macrophages to engulf budding crystals in mice  

作　　者：Huiling Chen Kaiqiang Hu Yaru Liang Yuqi Gao Chenye Zeng Kang Xu Xiaojin Shi Liyuan Li Yuemiao Yin Yi Qiao Ying Qiu Qingfei Liu Zhao Wang 

机构地区：[1]School of Pharmaceutical Sciences,Tsinghua University,Beijing 100084,China [2]Urology Department,Peking Union Medical College Hospital,Beijing 100730,China [3]School of Medicine,Tsinghua University,Beijing 100084,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第2期747-758,共12页药学学报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(81974503 and 81871095);the National Key R&D Program of China(2018YFC2000304);the Key International S&T Cooperation Program of China(2016YFE0113700);the European Union’s Horizon 2020 Research and Innovation Program(633589);the Natural Science Foundation of Beijing,China(7202096);the Tsinghua University independent research program(7191007,China)。

摘　　要：Although primary vesical calculi is an ancient disease,the mechanism of calculi formation remains unclear.In this study,we established a novel primary vesical calculi model with D,L-choline tartrate in mice.Compared with commonly used melamine and ethylene glycol models,our model was the only approach that induced vesical calculi without causing kidney injury.Previous studies suggest that proteins in the daily diet are the main contributors to the prevention of vesical calculi,yet the effect of fat is overlooked.To assay the relationship of dietary fat with the formation of primary vesical calculi,D,L-choline tartrate-treated mice were fed a high-fat,low-fat,or normal-fat diet.Genetic changes in the mouse bladder were detected with transcriptome analysis.A high-fat diet remarkably reduced the morbidity of primary vesical calculi.Higher fatty acid levels in serum and urine were observed in the high-fat diet group,and more intact epithelia in bladder were observed in the same group compared with the normal-and low-fat diet groups,suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure.Transcriptome analysis revealed that the macrophage differentiation-related gene C-X-C motif chemokine ligand 14(Cxcl14)was upregulated in the bladders of high-fat diet-fed mice compared with those of normal-or low-fat diet-fed mice,which was consistent with histological observations.The expression of CXCL14 significantly increased in the bladder in the high-fat diet group.CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages,which led to phagocytosis of budding crystals and prevented accumulation of calculi.In human bladder epithelia(HCV-29)cells,high fatty acid supplementation significantly increased the expression of CXCL14.Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi,which provides new ideas for the reduction of morbid

关 键 词：Primary vesical calculi Diet HIGH-FAT D L-Choline tartrate Macrophage CXCL14 Fatty acid UROTHELIUM 

分 类 号：R694.4[医药卫生—泌尿科学]