Oleate and eicosapentaenoic acid attenuate palmitate-induced inflammation and apoptosis in renal proximal tubular cell

Biochem Biophys Res Commun. 2010 Nov 12;402(2):265-71. doi: 10.1016/j.bbrc.2010.10.012. Epub 2010 Oct 16.


Free fatty acid (FFA)-bound albumin, which is filtrated through the glomeruli and reabsorbed into proximal tubular cells, is one of the crucial mediators of tubular damage in proteinuric kidney disease. In this study, we examined the role of each kind of FFA on renal tubular damage in vitro and tried to identify its molecular mechanism. In cultured proximal tubular cells, a saturated fatty acid, palmiate, increased the expression of monocyte chemoattractant protein-1 (MCP-1), but this effect was abrogated by co-incubation of monounsaturated fatty acid, oleate, or ω-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA). Palmitate led to intracellular accumulation of diacylglycerol (DAG) and subsequent activation of protein kinase C protein family. Among the several PKC inhibitors, rottlerin, a PKCθ inhibitor, prevented palmitate-induced MCP-1 expression via inactivation of NFB pathway. Overexpression of dominant-negative PKCθ also inhibited palmitate-induced activation of MCP-1 promoter. Furthermore, palmitate enhanced PKCθ-dependent mitochondrial apoptosis, which was also prevented by co-incubation with oleate or EPA through restoration of pro-survival Akt pathway. Moreover, oleate and EPA inhibited palmitate-induced PKCθ activation through the conversion of intracellular DAG to triglyceride with the restoration of diacylglycerol acyltransferase 2 expression. These results suggest that oleate and EPA have protective effects against the palmitate-induced renal tubular cell damage by inhibiting PKCθ activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Cytoprotection*
  • Diacylglycerol O-Acyltransferase / metabolism
  • Eicosapentaenoic Acid / pharmacology*
  • Humans
  • Inflammation / chemically induced*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / pathology
  • Mice
  • NF-kappa B / metabolism
  • Oleic Acid / pharmacology*
  • Palmitates / antagonists & inhibitors*
  • Palmitates / toxicity
  • Promoter Regions, Genetic / drug effects
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Protein Kinase C-theta
  • Proto-Oncogene Proteins c-akt / metabolism
  • Transcriptional Activation
  • Triglycerides / metabolism


  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Isoenzymes
  • NF-kappa B
  • Palmitates
  • Triglycerides
  • Oleic Acid
  • Eicosapentaenoic Acid
  • DGAT2 protein, mouse
  • Diacylglycerol O-Acyltransferase
  • Proto-Oncogene Proteins c-akt
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta