Reduced kidney lipoprotein lipase and renal tubule triglyceride accumulation in cisplatin-mediated acute kidney injury

Shenyang Li, K. Nagothu, G. Ranganathan, S.M. Ali, B. Shank, N. Gokden, S. Ayyadevara, J. Megysi, G. Olivecrona, S.S. Chugh, A.H. Kersten, D. Portilla

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptor-a (PPARa) activation attenuates cisplatin (CP)-mediated acute kidney injury by increasing fatty acid oxidation, but mechanisms leading to reduced renal triglyceride (TG) accumulation could also contribute. Here, we investigated the effects of PPARa and CP on expression and enzyme activity of kidney lipoprotein lipase (LPL) as well as on expression of angiopoietin protein-like 4 (Angptl4), glycosylphosphatidylinositol-anchored-HDL-binding protein (GPIHBP1), and lipase maturation factor 1 (Lmf1), which are recognized as important proteins that modulate LPL activity. CP caused a 40% reduction in epididymal white adipose tissue (WAT) mass, with a reduction of LPL expression and activity. CP also reduced kidney LPL expression and activity. Angptl4 mRNA levels were increased by ninefold in liver and kidney tissue and by twofold in adipose tissue of CP-treated mice. Western blots of two-dimensional gel electrophoresis identified increased expression of a neutral pI Angptl4 protein in kidney tissue of CP-treated mice. Immunolocalization studies showed reduced staining of LPL and increased staining of Angptl4 primarily in proximal tubules of CP-treated mice. CP also increased TG accumulation in kidney tissue, which was ameliorated by PPARa ligand. In summary, a PPARa ligand ameliorates CP-mediated nephrotoxicity by increasing LPL activity via increased expression of GPHBP1 and Lmf1 and by reducing expression of Angptl4 protein in the proximal tubule.
Original languageEnglish
Pages (from-to)F437-F448
JournalAmerican Journal of Physiology : Renal Physiology
Volume303
Issue number3
DOIs
Publication statusPublished - 2012

Keywords

  • adipose-tissue
  • human adipocytes
  • ppar-alpha
  • induced nephrotoxicity
  • density-lipoprotein
  • failure
  • metabolism
  • expression
  • mechanisms
  • deficiency

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