Paradoxical reduction of atherosclerosis in apoE-deficient mice with obesity-related type 2 diabetes

L. G. Lyngdorf, S. Gregersen, A. Daugherty, E. Falk

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Objective: The effect of obesity and insulin resistance on the development of atherosclerosis was evaluated in apoE-deficient (ApoE-/-) mice. A previously described obesity model, in which the hypothalamic satiety center can be destroyed by a single gold thioglucose (GTG) injection, was used. To evaluate the effect of starvation on atherosclerosis ApoE-/- mice were food-restricted with 25% less chow than ad libitum-fed control mice. Methods: Sixty-eight ApoE-/- mice were allocated into a control group (n=20), a GTG-injected group (n=28), and a food-restricted group (n=20). The control and food-restricted mice were injected with saline instead of GTG. The control and GTG-injected mice had free access to food, and all mice had free access to water during the study period. Results: After 4 months, the GTG-injected mice were significantly overweight (mean body weight (g): 33±2.11 vs. 23±0.24 and 17±0.31 in control and food-restricted mice, respectively), obese, hypertriglyceridemic, insulin-resistant, hyperinsulinemic (mean plasma insulin (ng/ml): 2.45 and 0.43 in obese and control mice, respectively), and hyperglycemic (mean plasma glucose (mmol/l): 11.03 and 7.80 in obese and control mice, respectively). Unexpectedly, these obese and diabetic mice developed significantly less atherosclerosis compared with lean non-diabetic control mice. Food-restricted mice also developed less atherosclerosis compared to control mice. Conclusions: These findings may question the usefulness of mouse models in studying the relation of obesity-related type 2 diabetes to atherosclerosis and also the relevance of results obtained in apoE-/- mice with reduced weight gain during intervention.

Original languageEnglish
Pages (from-to)854-862
Number of pages9
JournalCardiovascular Research
Issue number4
StatePublished - Oct 1 2003

Bibliographical note

Funding Information:
Ji Zhou, Trine-Line Korsholm, Mette Olesen and Won Yong Kim are thanked for their helpfulness during the study. The Department of Clinical Biochemistry, Skejby Sygehus, is thanked for the determination of plasma lipids (Jan Møller). A special thank is given to Sandra Schreyer for helpful scientific advise. This study was supported by: the Danish Heart Foundation, the Danish Medical Research Council, Murermester Laurits Peter Christensen and wife Sigrid Christensen’s Foundation, and Elin Holm Foundation.


  • Apolipoprotein E deficient mice
  • Atherosclerosis
  • Food restriction
  • Gold thioglucose
  • Insulin resistance
  • Obesity
  • Type 2 diabetes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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