Druggability of lipid metabolism modulation against renal fibrosis

Acta Pharmacol Sin. 2022 Mar;43(3):505-519. doi: 10.1038/s41401-021-00660-1. Epub 2021 May 14.

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: anti-renal fibrosis; drug targets; fatty acid oxidation; lipid metabolism; noncoding RNA.

Publication types

  • Review

MeSH terms

  • Animals
  • CD36 Antigens / metabolism
  • Carnitine O-Palmitoyltransferase / metabolism
  • Epithelial Cells / pathology
  • Fatty Acids / metabolism
  • Fibrosis / pathology*
  • Inflammation / pathology
  • Kidney / physiology
  • Lipid Metabolism / drug effects*
  • Lipid Metabolism / physiology*
  • MicroRNAs / metabolism
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • RNA, Untranslated / metabolism
  • Renal Insufficiency, Chronic / pathology*
  • Sterol Regulatory Element Binding Proteins / metabolism
  • Transforming Growth Factor beta / drug effects
  • Transforming Growth Factor beta / metabolism

Substances

  • CD36 Antigens
  • Fatty Acids
  • MicroRNAs
  • Peroxisome Proliferator-Activated Receptors
  • RNA, Untranslated
  • Sterol Regulatory Element Binding Proteins
  • Transforming Growth Factor beta
  • Carnitine O-Palmitoyltransferase