Fatty acid binding protein 3 as a potential mediator for diabetic nephropathy in eNOS deficient mouse

Biochem Biophys Res Commun. 2014 Nov 28;454(4):531-6. doi: 10.1016/j.bbrc.2014.10.121. Epub 2014 Oct 30.

Abstract

In human diabetic nephropathy, glomerular injury was found to comprise lipid droplets, suggesting that abnormal lipid metabolism might take place in the development of diabetic glomerular injury. However, its precise mechanism remains unclear. Fatty acid binding protein (FABP) is currently considered as a key molecule for lipid metabolism. Since diabetic eNOS knockout (KO) mouse is considered to be a good model for human diabetic nephropathy, we here investigated whether FABP could mediate glomerular injury in this model. We found that glomerular injuries were associated with inflammatory processes, such as macrophage infiltration and MCP-1 induction. Microarray assay with isolated glomeruli revealed that among 10 isoforms in FABP family, FABP3 mRNA was most highly expressed in diabetic eNOSKO mice compared to non-diabetic eNOSKO mice. FABP3 protein was found to be located in the mesangial cells. Overexpression of FABP3 resulted in a greater response to palmitate, a satulated FA, to induce MCP-1 in the rat mesangial cells. In turn, the heart, a major organ for FABP3 protein in normal condition, failed to alter its expression level under diabetic condition in either wild type or eNOSKO mice. In conclusion, FABP3 is induced in the mesangial cells and likely a mediator to induce MCP-1 in the diabetic nephropathy.

Keywords: Advanced diabetic nephropathy; Endothelial; FABP; Fatty acid; Inflammation; Nitric oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL2 / metabolism
  • Diabetic Nephropathies / metabolism*
  • Fatty Acid Binding Protein 3
  • Fatty Acid-Binding Proteins / genetics
  • Fatty Acid-Binding Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Nitric Oxide Synthase Type III / deficiency*
  • Nitric Oxide Synthase Type III / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Fabp3 protein, mouse
  • Fatty Acid Binding Protein 3
  • Fatty Acid-Binding Proteins
  • RNA, Messenger
  • Nitric Oxide Synthase Type III