Addition of dietary fat to cholesterol in the diets of LDL receptor knockout
mice: effects on plasma insulin, lipoproteins, and atherosclerosis.
Authors Wu L, Vikramadithyan R, Yu S, Pau C, Hu Y, Goldberg IJ, Dansky HM
Submitted By Submitted Externally on 3/4/2015
Status Published
Journal Journal of lipid research
Year 2006
Date Published 10/1/2006
Volume : Pages 47 : 2215 - 2222
PubMed Reference 16840797
Abstract 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. Ldlr(-/-) mice fed a high-fat diet developed obesity, mild
hyperglycemia, hyperinsulinemia, and hypertriglyceridemia. Quantitative and
qualitative assessments of atherosclerosis were unchanged in diabetic Ldlr(-/-)
mice fed a high-fat diet compared with 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 that when lipoprotein profiles are similar, addition of fat to a
cholesterol-rich diet does not increase atherosclerotic lesion formation in
Ldlr(-/-) mice.

Investigators with authorship
Ira GoldbergNew York University School of Medicine