The renoprotective effect of foods high in omega-3 fatty acids in a rat model of type 1 diabetes
Thesis (Ph.D.)--Georgetown University, 2009.; Includes bibliographical references.; Text (Electronic thesis) in PDF format. Background: Dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) have demonstrated anti-inflammatory actions that are beneficial in several diseases, but their potential benefit and mechanism of action in the treatment of diabetic nephropathy is not yet established.; Methods: Type 1 diabetes was induced in Sprague-Dawley rats using a single injection of streptozotocin (STZ), and animals were divided into five groups; non-diabetic, diabetic eating unsupplemented chow, diabetic eating n-3 PUFA rich canola or walnut diets, and diabetic eating n-6 PUFA rich corn oil diet. For all supplemental diets, added fat contributed 40% of calories, and animals were fed ad libitum. In the first study ("prevention" study) supplementation started 2 weeks before induction of diabetes, while in the second study ("delayed-treatment" study) supplementation started 7 weeks after induction of diabetes. The duration of the studies were 30 weeks of diabetes (prevention study), or 45 weeks (delayed-treatment study). Various measures of kidney damage were assessed including albuminuria, and glomerular and tubular damage, and inflammatory markers including renal TGF-b, IL-6 and MCP-1.; Results: In both studies, the n-3 PUFA and n-6 PUFA rich diets prevented the increases in urine albumin excretion (UAE) and blood pressure, and the development of glomerulosclerosis, and tubulointerstitial fibrosis characteristic of diabetic kidney disease. In most cases, the inflammatory markers (cytokines TGF-b, MCP-1, and IL-6) observed in kidneys of the diabetic rats fed normal chow were reduced with both n-3 and n-6 PUFA rich diet. The lack of inflammation in kidneys from rats fed n-3 PUFA rich diets prevented the increase in collagen I and IV, and a loss of nephrin and nestin typically associated with diabetic renal disease.; Conclusion: Dietary n-3 and n-6 PUFA rich foods appear to be beneficial in both the prevention and treatment of diabetic renal complications through suppression of pro-inflammatory cytokines. Further studies are needed to determine the amount of n-3 or n-6 PUFA needed to obtain these results in humans.
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