C57BL/6J and A/J mice fed a high-fat diet delineate components of metabolic syndrome.
OBJECTIVE
The aim of this study was to assess the suitability of A/J and C57BL/6J mice of both sexes as models of some components of the human metabolic syndrome (MetS) under nutritional conditions more comparable with the actual worldwide diet responsible for the increased incidence of the MetS.


METHODS
We fed large cohorts (n = 515) of two strains of mice, A/J and the C57BL/6J, and of both sexes a high-fat diet (HFD; 60% fat) that, in contrast with most previous reports using saturated fats, was enriched in mono- and polyunsaturated fatty acids, thus more closely mimicking most Western diets, or a control diet (10% fat), for 20 weeks.


RESULTS
In sharp contrast to previous reports, weight gain and hyperleptinemia were similar in both strains and sexes. Hyperinsulinemia, glucose tolerance, insulin resistance, and hypercholesterolemia were observed, although with important differences between strains and sexes. A/J males displayed severely impaired glucose tolerance and insulin resistance. However, in contrast with C57BL6/J mice, which displayed overt type 2 diabetes, A/J mice of both sexes remained normoglycemic.


CONCLUSIONS
With important differences in magnitude and time course, the phenotypic and metabolic characteristics of both strains and both sexes on this HFD demonstrate that these models are very useful for identifying the mechanisms underlying progression or resistance to subsequent type 2 diabetes.
Gallou-Kabani
Catherine
C
Institut National de la Santé et de la Recherche Médicale, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, Faculté de Médecine, Hôpital Necker-Enfants Malades, Paris, France.
Vigé
Alexandre
A
Gross
Marie-Sylvie
MS
Rabès
Jean-Pierre
JP
Boileau
Catherine
C
Larue-Achagiotis
Christiane
C
Tomé
Daniel
D
Jais
Jean-Philippe
JP
Junien
Claudine
C
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D004195:Disease Models, Animal; D004435:Eating / Q000502:physiology; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D011247:Pregnancy; D013047:Specific Pathogen-Free Organisms; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004041:Dietary Fats; D005229:Fatty Acids, Monounsaturated; D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D002784:Cholesterol