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Animal Models

Butyrate restores HFD-induced adaptations in brain function and metabolism in mid-adult obese mice

International Journal of Obesity volume 41, pages 935–944 (2017)Cite this article

Subjects

Abstract

Objective:

Midlife obesity affects cognition and increases risk of developing dementia. Recent data suggest that intake of the short chain fatty acid butyrate could improve memory function, and may protect against diet-induced obesity by reducing body weight and adiposity.

Subjects:

We examined the impact of a high-fat diet (HFD) followed by intervention with 5% (w/w) dietary butyrate, on metabolism, microbiota, brain function and structure in the low-density-lipoprotein receptor knockout (LDLr−/−) mouse model in mid and late life.

Results:

In mid-adult mice, 15 weeks of HFD-induced adiposity, liver fibrosis and neuroinflammation, increased systolic blood pressure and decreased cerebral blood flow, functional connectivity assessed with neuroimaging. The subsequent 2 months butyrate intervention restored these detrimental effects to chow-fed control levels. Both HFD and butyrate intervention decreased variance in fecal microbiota composition. In late-adult mice, HFD showed similar detrimental effects and decreased cerebral white and gray matter integrity, whereas butyrate intervention attenuated only metabolic parameters.

Conclusion:

HFD induces detrimental effects in mid- and late-adult mice, which can be attenuated by butyrate intervention. These findings are consistent with reported associations between midlife obesity and cognitive impairment and dementia in humans. We suggest that butyrate may have potential in prevention and treatment of midlife obesity.

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Acknowledgements

We thank Andor Veltien, Anouk Tengeler, Bram Geenen, Jos Dederen, Tim Emmerzaal for their great scientific support. We would like to acknowledge Nicole Bakker and the bio-technicians at TNO Leiden, PRIME and the Central Animal Laboratory of the Radboud university medical center for taking excellent care of our mice.

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Author notes

  1. P Y Wielinga and A J Kiliaan: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Centre, Nijmegen, The Netherlands

    I A C Arnoldussen, M Wiesmann, C E Pelgrim, E M Wielemaker & A J Kiliaan

  2. Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Leiden, The Netherlands

    W van Duyvenvoorde, R Kleemann & P Y Wielinga

  3. Department of Microbiology and Systems Biology, Netherlands Organisation for Applied Scientific Research (TNO), Zeist, The Netherlands

    P L Amaral-Santos, L Verschuren & B J F Keijser

  4. Department of Radiology and Nuclear Medicines, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Centre, Nijmegen, The Netherlands

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Correspondence to A J Kiliaan.

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Arnoldussen, I., Wiesmann, M., Pelgrim, C. et al. Butyrate restores HFD-induced adaptations in brain function and metabolism in mid-adult obese mice. Int J Obes 41, 935–944 (2017). https://doi.org/10.1038/ijo.2017.52

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