Journal of Lipid Research, Vol 31, 1219-1228, Copyright © 1990 by Lipid Research, Inc.
Effects of fish oil on glomerular function in rats with diabetes mellitus
AK Sinha, LA Scharschmidt, R Neuwirth, H Holthofer, N Gibbons, CM Arbeeny and D Schlondorff
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10467.
The mechanisms responsible for hyperfiltration in diabetes mellitus (DM) as
well as for the initiation and progression of diabetic nephropathy are not
fully elucidated. Enhanced prostaglandin E2 (PGE2) production has been
invoked in the former and thromboxane (TXB2) and hyperlipidemia in the
latter. Fish oil (FO)-enriched diets can favorably alter eicosanoid
synthesis and serum lipid profiles. We therefore examined the effects of a
FO-enriched diet on glomerular filtration (GFR), proteinuria, glomerular
eicosanoid production, and serum lipids in rats with streptozotocin-induced
DM (STZ-DM). Groups of 5-8 rats with STZ-DM were maintained on low insulin
and then pair-fed with isocaloric diets enriched with either FO (20% w/w)
or beef tallow (BT; 20% w/w). GFR was determined in the same animals at
onset of diet and after 8 and 20 weeks on the respective diets by
[14C]inulin clearance using implanted osmotic minipumps each time.
Significant hyperfiltration was present initially and GFR did not change on
either diet for 20 weeks, in spite of a significant and greater than 50%
decrease in all prostaglandins (PGE2, TXB2, PGF2 alpha, 6-keto, PGF1 alpha)
produced by glomeruli isolated from DM/FO as compared to DM/BT or control
rats. FO diet completely corrected the hypertriglyceridemia of diabetes and
significantly reduced the mild and early proteinuria of DM. The decrease in
proteinuria and the correction of hyperlipidemia of DM by a FO-enriched
diet may be beneficial in the long term not only for the development of
diabetic glomerulopathy, but also for the accelerated atherosclerosis of
DM.
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