title: Omacor, n-3 polyunsaturated fatty acid, attenuated albuminuria and renal dysfunction with decrease of SREBP-1 expression and triglyceride amount in the kidney of type II diabetic animals.
abstract: BACKGROUND
  We assumed that n-3 polyunsaturated fatty acid (n-3 PUFA) would attenuate the tissue dyslipidemic condition through suppression of sterol regulatory element-binding protein (SREBP-1) in the kidney and would prevent renal progression in diabetic animals.
  
  
  METHODS
  We gavaged Omacor, composed of docosahexaenoic acid and eicosapentaenoic acid, to db/db mice for 2 weeks (0.2 g/100 g/day). We measured the markers of renal function, triglyceride amount and expressions of SREBP-1, liver X-activated receptor alpha (LXRalpha), collagen IV and TGFbeta-1 in kidney lysate, and performed immunohistochemical staining for SREBP-1, desmin and WT-1 in the renal sections. We measured collagen IV in primary mesangial cells cultured with high glucose media (25 mM), both with and without a transient transfection of small interfering RNA (siRNA) SREBP-1.
  
  
  RESULTS
  Omacor decreased the concentration of serum free fatty acid, and the amount of renal triglyceride, which was associated with decreased expression of SREBP-1 in the kidney, albuminuria and renal dysfunction in db/db mice. Omacor attenuated the expansion of mesangial matrix and the expression of desmin, preserved the WT-1 positive cells, and inhibited the phosphorylation of nuclear factor kappaB in renal tissue. In mesangial cells cultured in high glucose media, the suppression of SREBP-1 expression decreased the collagen IV in the cells.
  
  
  CONCLUSIONS
  Our study results demonstrated that n-3 PUFA prevented renal progression with attenuation of SREBP-1 and reduction of triglyceride in the diabetic kidney. This suggests that the regulation of dyslipidemic signals in the kidney could be a possible mechanism by which PUFA preserves renal function in the diabetic condition.
authors.affiliation: 1Department of Internal Medicine, Seoul National University College of Medicine.
authors.forename: Ho Jun
authors.initials: HJ
authors.lastname: Chin
authors.forename: Yan Yan
authors.initials: YY
authors.lastname: Fu
authors.forename: Jeong Myung
authors.initials: JM
authors.lastname: Ahn
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Na
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
authors.forename: Suhnggwon
authors.initials: S
authors.lastname: Kim
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Chae
mesh_terms: D000419:Albuminuria / Q000188:drug therapy*; D000818:Animals; D024141:Collagen Type IV / Q000032:analysis; D003893:Desmin / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004281:Docosahexaenoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000737:chemistry* / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D051780:Sterol Regulatory Element Binding Protein 1 / Q000032:analysis*; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D014280:Triglycerides / Q000032:analysis*
chemical_list: D024141:Collagen Type IV; D003893:Desmin; D004338:Drug Combinations; D016328:NF-kappa B; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D053773:Transforming Growth Factor beta1; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C405603:Omacor