biostudies-literatureChen Ythe longitudinal subproject of Naval Engineering UniversityNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (National Science Foundation of China)572https://www.ebi.ac.uk/biostudies/studies/S-EPMC8175732biostudies-literatureUnknown12(6)Kidney fibrosis is a hallmark of chronic kidney disease (CKD) progression that is caused by tubular injury and dysregulated lipid metabolism. Genetic abolition fatty acid-binding protein 4 (FABP4), a key lipid transporter, has been reported to suppress kidney interstitial fibrosis. However, the role and underlying mechanism of chemical inhibition of FABP4 in fibrotic kidney have not been well-documented. Here, we examined preemptive the effect of a FABP4 inhibitor, BMS309403, on lipid metabolism of tubular epithelial cells (TECs) and progression of kidney fibrosis. The expression of FABP4 was significantly elevated, concomitated with the accumulation of lipid droplets in TECs during kidney fibrosis. Treatment with BMS309403 alleviated lipid deposition of TECs, as well as interstitial fibroCell death & diseasePre-emptive pharmacological inhibition of fatty acid-binding protein 4 attenuates kidney fibrosis by reprogramming tubular lipid metabolism.PMC817573281800603Song KHuang YYan QChen YZhang LGao HZhang CDai YfalsePre-emptive pharmacological inhibition of fatty acid-binding protein 4 attenuates kidney fibrosis by reprogramming tubular lipid metabolism.Kidney fibrosis is a hallmark of chronic kidney disease (CKD) progression that is caused by tubular injury and dysregulated lipid metabolism. Genetic abolition fatty acid-binding protein 4 (FABP4), a key lipid transporter, has been reported to suppress kidney interstitial fibrosis. However, the role and underlying mechanism of chemical inhibition of FABP4 in fibrotic kidney have not been well-documented. Here, we examined preemptive the effect of a FABP4 inhibitor, BMS309403, on lipid metabolism of tubular epithelial cells (TECs) and progression of kidney fibrosis. The expression of FABP4 was significantly elevated, concomitated with the accumulation of lipid droplets in TECs during kidney fibrosis. Treatment with BMS309403 alleviated lipid deposition of TECs, as well as interstitial fibro2021-01-01T00:00:00Z2021 Jun2025-04-19T09:01:11.871Z2022-02-10T13:54:42.515ZS-EPMC81757323408351310.1038/s41419-021-03850-1