Print Email Facebook Twitter Butyrate restores HFD-induced adaptations in brain function and metabolism in mid-adult obese mice Title Butyrate restores HFD-induced adaptations in brain function and metabolism in mid-adult obese mice Author Arnoldussen, I.A.C. Wiesmann, M. Pelgrim, C.E. Wielemaker, E.M. van Duyvenvoorde, W. Amaral-Santos, P.L. Verschuren, L. Keijser, B.J.F. Heerschap, A. Kleemann, R. Wielinga, P.Y. Kiliaan, A.J. Publication year 2017 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. Subject LifeMHR - Metabolic Health ResearchELSS - Earth, Life and Social SciencesBiomedical InnovationHealthHealthy Living To reference this document use: http://resolver.tudelft.nl/uuid:9d3e914e-fdbc-41e6-b592-6d8692e9d4ae DOI https://doi.org/10.1038/ijo.2017.52 TNO identifier 807266 Source International Journal of Obesity, 41 (6), 935-944 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.