The High-Fat Diet–Fed Mouse

A Model for Studying Mechanisms and Treatment of Impaired Glucose Tolerance and Type 2 Diabetes

  1. Maria Sörhede Winzell and
  2. Bo Ahrén
  1. Department of Medicine, Biomedical Center, Lund University, Lund, Sweden
  1. Address correspondence and reprint requests to Maria Sörhede Winzell, Dept. of Medicine, Biomedical Center (BMC), B11, S-221 84 Lund, Sweden. E-mail: maria.sorhede_winzell{at}


This study characterizes the high-fat diet–fed mouse as a model for impaired glucose tolerance (IGT) and type 2 diabetes. Female C57BL/6J mice were fed a high-fat diet (58% energy by fat) or a normal diet (11% fat). Body weight was higher in mice fed the high-fat diet already after the first week, due to higher dietary intake in combination with lower metabolic efficiency. Circulating glucose increased after 1 week on high-fat diet and remained elevated at a level of ∼1 mmol/l throughout the 12-month study period. In contrast, circulating insulin increased progressively by time. Intravenous glucose challenge revealed a severely compromised insulin response in association with marked glucose intolerance already after 1 week. To illustrate the usefulness of this model for the development of new treatment, mice were fed an orally active inhibitor of dipeptidyl peptidase-IV (LAF237) in the drinking water (0.3 mg/ml) for 4 weeks. This normalized glucose tolerance, as judged by an oral glucose tolerance test, in association with augmented insulin secretion. We conclude that the high-fat diet–fed C57BL/6J mouse model is a robust model for IGT and early type 2 diabetes, which may be used for studies on pathophysiology and development of new treatment.


  • This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Servier.

    B.A. is an advisory panel member for and has received grant support from Novartis Pharmaceuticals.

    • Accepted May 31, 2004.
    • Received March 11, 2004.
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