Review Article

Druggability of lipid metabolism modulation against renal fibrosis

Yuan-yuan Chen1, Xiao-guang Chen1, Sen Zhang1
1 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union medical college, Beijing 100050, China
Correspondence to: Xiao-guang Chen: chxg@imm.ac.cn, Sen Zhang: zhangs@imm.ac.cn,
DOI: 10.1038/s41401-021-00660-1
Received: 11 November 2020
Accepted: 16 March 2021
Advance online: 14 May 2021

Abstract

Renal fibrosis contributes to progressive damage to renal structure and function. It is a common pathological process as chronic kidney disease develops into kidney failure, irrespective of diverse etiologies, and eventually leads to death. However, there are no effective drugs for renal fibrosis treatment at present. Lipid aggregation in the kidney and consequent lipotoxicity always accompany chronic kidney disease and fibrosis. Numerous studies have revealed that restoring the defective fatty acid oxidation in the kidney cells can mitigate renal fibrosis. Thus, it is an important strategy to reverse the dysfunctional lipid metabolism in the kidney, by targeting critical regulators of lipid metabolism. In this review, we highlight the potential “druggability” of lipid metabolism to ameliorate renal fibrosis and provide current pre-clinical evidence, exemplified by some representative druggable targets and several other metabolic regulators with anti-renal fibrosis roles. Then, we introduce the preliminary progress of noncoding RNAs as promising anti-renal fibrosis drug targets from the perspective of lipid metabolism. Finally, we discuss the prospects and deficiencies of drug targeting lipid reprogramming in the kidney.
Keywords: lipid metabolism; anti-renal fibrosis; drug targets; fatty acid oxidation; noncoding RNA

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