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.
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.
Chin
Ho Jun
HJ
1Department of Internal Medicine, Seoul National University College of Medicine.
Fu
Yan Yan
YY
Ahn
Jeong Myung
JM
Na
Ki Young
KY
Kim
Yon Su
YS
Kim
Suhnggwon
S
Chae
Dong-Wan
DW
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*
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