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J. Lipid Res.
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A more recent version of this article appeared on October 1, 2006

Papers In Press, published online ahead of print July 13, 2006
J. Lipid Res., doi:10.1194/jlr.M600146-JLR200
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Submitted on March 29, 2006
Revised on June 14, 2006
Accepted on July 12, 2006

Addition of dietary fat to cholesterol in the diets of LDL receptor knockout mice: Effects on plasma insulin, lipoproteins and atherosclerosis

Lan Wu, Reeba Vikramadithyan, Shuiqing Yu, Clara Pau, Yunying Hu, Ira J. Goldberg, and Hayes M. Dansky

Experimental Medicine, Merck and Co. Inc, Rahway, NJ 07065

Corresponding Author: hayes_dansky{at}merck.com

The factors underlying cardiovascular risk in patients with diabetes have not been clearly elucidated. Efforts to study this in mice have been hindered because the usual atherogenic diets that contain fat and cholesterol also lead to obesity and insulin resistance. We compared plasma glucose, insulin and atherosclerotic lesion formation in LDL receptor knockout (Ldlr-/-) mice fed diets with varying fat and cholesterol content that induced similar lipoprotein profiles. High fat diet fed Ldlr-/- mice developed obesity, mild hyperglycemia, hyperinsulinemia, and hypertriglyceridemia. Quantitative and qualitative assessments of atherosclerosis were unchanged in high fat diet fed diabetic Ldlr-/- mice compared to lean nondiabetic control mice after 20 weeks of diet. Although one group of mice fed diets for 40 weeks had larger lesions at the aortic root, this was associated with a more atherogenic lipoprotein profile. The presence of a human aldose reductase transgene had no effect on atherosclerosis in fat fed Ldlr-/- mice with mild diabetes. Our data suggest when lipoprotein profiles are similar, addition of fat to a cholesterol-rich diet does not increase atherosclerotic lesion formation in Ldlr-/- mice.


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