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A free-choice high-fat high-sugar diet induces glucose intolerance and insulin unresponsiveness to a glucose load not explained by obesity

International Journal of Obesity volume 35, pages 595–604 (2011)Cite this article

Subjects

Abstract

Objectives:

In diet-induced obesity, it is not clear whether impaired glucose metabolism is caused directly by the diet, or indirectly via obesity. This study examined the effects of different free-choice, high-caloric, obesity-inducing diets on glucose metabolism. In these free-choice diets, saturated fat and/or a 30% sugar solution are provided in an addition to normal chow pellets.

Method:

In the first experiment, male rats received a free-choice high-fat high-sugar (HFHS), free-choice high-fat (HF) or a chow diet. In a second experiment, male rats received a free-choice high-sugar (HS) diet or chow diet. For both experiments, after weeks 1 and 4, an intravenous glucose tolerance test was performed.

Results:

Both the HFHS and HF diets resulted in obesity with comparable plasma concentrations of free fatty acids. Interestingly, the HF diet did not affect glucose metabolism, whereas the HFHS diet resulted in hyperglycemia, hyperinsulinemia and in glucose intolerance because of a diminished insulin response. Moreover, adiposity in rats on the HF diet correlated positively with the insulin response to the glucose load, whereas adiposity in rats on the HFHS diet showed a negative correlation. In addition, total caloric intake did not explain differences in glucose tolerance. To test whether sugar itself was crucial, we next performed a similar experiment in rats on the HS diet. Rats consumed three times as much sugar when compared with rats on the HFHS diet, which resulted in obesity with basal hyperinsulinemia. Glucose tolerance, however, was not affected.

Conclusion:

Together, these results suggest that not only obesity or total caloric intake, but the diet content also is crucial for the glucose intolerance that we observed in rats on the HFHS diet.

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Acknowledgements

We thank Dr JM Chou-Green for English editing and Drs MJM Serlie and M Soeters for critically reading the manuscript. This research was supported by the Netherlands Organization for Scientific Research (ZonMw 916.56.020).

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Authors and Affiliations

  1. Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands

    S E la Fleur, M C M Luijendijk, A J van Rozen & R A H Adan

  2. Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    S E la Fleur & A Kalsbeek

  3. Netherlands Institute for Neurosciences, Amsterdam, The Netherlands

    A Kalsbeek

Authors
  1. S E la Fleur
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  2. M C M Luijendijk
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  3. A J van Rozen
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Correspondence to S E la Fleur.

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la Fleur, S., Luijendijk, M., van Rozen, A. et al. A free-choice high-fat high-sugar diet induces glucose intolerance and insulin unresponsiveness to a glucose load not explained by obesity. Int J Obes 35, 595–604 (2011). https://doi.org/10.1038/ijo.2010.164

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