title: Paradoxical reduction of atherosclerosis in apoE-deficient mice with obesity-related type 2 diabetes.
abstract: 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.
authors.affiliation: Department of Cardiology and Institute of Experimental Clinical Research, Aarhus University Hospital (Skejby Sygehus), DK-8200 Aarhus N, Denmark. linegrly@yahoo.com
authors.forename: L G
authors.initials: LG
authors.lastname: Lyngdorf
authors.forename: S
authors.initials: S
authors.lastname: Gregersen
authors.forename: A
authors.initials: A
authors.lastname: Daugherty
authors.forename: E
authors.initials: E
authors.lastname: Falk
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D006051:Aurothioglucose; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005508:Food Deprivation; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009206:Myocardium / Q000473:pathology; D009765:Obesity / Q000378:metabolism*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D006051:Aurothioglucose; D002784:Cholesterol