Omacor(R), 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

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. 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. 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. 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.