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Metabolic and behavioral responses to high-fat feeding in mice selectively bred for high wheel-running activity

International Journal of Obesity volume 32, pages 1566–1575 (2008)Cite this article

Abstract

Objective:

Increased dietary fat intake is a precipitating factor for the development of obesity and associated metabolic disturbances. Physically active individuals generally have a reduced risk of developing these unhealthy states, but the underlying mechanisms are poorly understood. In the present study, we investigated the effects of feeding a high-fat diet (HFD) on obesity development and fuel homeostasis in male and female mice with a trait for increased physical activity and in their controls.

Methods:

Male and female mice selectively bred for a high level of wheel running behavior over 30 generations and nonselected controls (background strain Hsd:ICR) were maintained on a standard lab chow high-carbohydrate diet (HCD) or on an HFD (60% fat). Food intake, body weight, indirect calorimetry parameters, spontaneous locomotor activity and several hormones relevant to metabolism and energy balance were measured.

Results:

On HFD, mice reduced food intake and increased body fat mass and plasma leptin levels, with the notable exception of the selected females, which increased their ingested calories without any effects on body mass or plasma leptin levels. In addition, they had an elevated daily energy expenditure (DEE), increased spontaneous cage activity (∼700% relative to controls) and higher resting metabolic rate (RMR) on the HFD compared with feeding the HCD. The selected males also had a higher DEE compared with controls, but no interaction with diet was observed. On HCD, adiponectin levels were higher in selected male, but not female, mice relative to controls. A marked increase in the level of plasma adiponectin was observed on the HFD in selected females, an effect of diet that was not observed in selected males.

Conclusion:

Genetically based high locomotor activity renders female, but not male, mice resistant to HFD-induced obesity by alterations in behavioral, endocrine and metabolic traits that facilitate fat utilization rather than limiting HFD intake.

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Acknowledgements

We thank G Overkamp and J Bruggink for expert technical assistance. This work was supported primarily by a career development grant from the Dutch Diabetes Foundation (to G van Dijk). Additional support was provided by grants from the US National Science Foundation (to T Garland), most recently IOB-0543429. The authors would like to commemorate Prof GH Visser, who inspired collaborations leading to this manuscript. Henk Visser passed away on 3 June 2007. He was a great friend and colleague and is deeply missed.

Author information

Authors and Affiliations

  1. Center for Behavior and Neurosciences, Animal Behavior Unit, University of Groningen, Groningen, the Netherlands

    L M Vaanholt, K A Schubert & G H Visser

  2. Department of Integrative Physiology, Institute for Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland

    L M Vaanholt

  3. Center for Behavior and Neurosciences, Neuroendocrinology Unit, University of Groningen, Groningen, the Netherlands

    I Jonas, M Doornbos & G van Dijk

  4. Center for Behavior and Neurosciences, Molecular Neurobiology Unit, University of Groningen, Groningen, the Netherlands

    C Nyakas

  5. Institute of Sport Sciences, Nutrition and Physical Activity Unit , Semmelweis University, Budapest, Hungary

    C Nyakas

  6. Department of Biology, University of California, Riverside, USA

    T Garland Jr

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  1. L M Vaanholt
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  2. I Jonas
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Correspondence to G van Dijk.

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Vaanholt, L., Jonas, I., Doornbos, M. et al. Metabolic and behavioral responses to high-fat feeding in mice selectively bred for high wheel-running activity. Int J Obes 32, 1566–1575 (2008). https://doi.org/10.1038/ijo.2008.136

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