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Long-Term, Fructose-Induced Metabolic Syndrome-Like Condition Is Associated with Higher Metabolism, Reduced Synaptic Plasticity and Cognitive Impairment in Octodon degus

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Abstract

There has been a progressive increase in the incidence of fructose-induced metabolic disorders, such as metabolic syndrome (MetS). Moreover, novel evidence reported negative effects of high-fructose diets in brain function. This study was designed to evaluate for the first time the effects of long-term fructose consumption (LT-FC) on the normal ageing process in a long-lived animal model rodent, Octodon degus or degu. Moreover, we could replicate human sugar consumption behaviour over time, leading us to understand then the possible mechanisms by which this MetS-like condition could affect cognitive abilities. Our results support that 28 months (from pup to adulthood) of a 15% solution of fructose induced clinical conditions similar to MetS which includes an insulin-resistance scenario together with elevated basal metabolic rate and non-alcoholic fatty liver disease. Additionally, we extended our analysis to evaluate the impact of this MetS-like condition on the functional and cognitive brain processes. Behavioural test suggests that fructose-induced MetS-like condition impair hippocampal-dependent and independent memory performance. Moreover, we also reported several neuropathological events as impaired hippocampal redox balance, together with synaptic protein loss. These changes might be responsible for the alterations in synaptic plasticity and transmitter release observed in these cognitively impaired animals. Our results indicate that LT-FC induced several facets of MetS that eventually could trigger brain disorders, in particular, synaptic dysfunction and reduced cognition.

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Acknowledgements

This work was supported by a postdoctoral grant from Fondo Nacional de Desarollo Científico y Tecnológico (FONDECYT) N° 3140395 to DSR. PC was supported by FONDECYT N° 11160651. MAA was supported by FONDECYT N°1150327. DC was supported by FONDECYT N° 11171001. NCI was supported by FONDECYT N° 1160724 and grants from the Basal Centre of Excellence in Science and Technology (CONICYT-PFB12/2007) and AFB 170005. In addition, a grant from CAPES-CONICYT FB 0002-2014 (Line 3) was awarded to FB. We thank G. Cavieres for assistance with Basal metabolic rate records, C. Céspedes for assistance with blood pressure measurements and J. Rios for assistance with liver histopathology analysis.

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Authors and Affiliations

  1. Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 6513677, Santiago, Chile

    Daniela S. Rivera, Carolina B. Lindsay, Juan F. Codocedo, Marco A. Arrese, Carlos P. Vio & Nibaldo C. Inestrosa

  2. Departamento de Ecología and Center of Applied Ecology and Sustainability (CAPES), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 6513677, Santiago, Chile

    Daniela S. Rivera & Francisco Bozinovic

  3. Servicio de Anatomía Patológica, Hospital Clínico de la Universidad de Chile, Santiago, Chile

    Laura E. Carreño

  4. Departamento de Gastroenterología, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

    Daniel Cabrera & Marco A. Arrese

  5. Departamento de Ciencias Químicas y Biológicas, Facultad de Salud, Santiago, Chile, Universidad Bernardo O’Higgins, Santiago, Chile

    Daniel Cabrera

  6. Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile

    Carlos P. Vio & Nibaldo C. Inestrosa

  7. Centro UC-Síndrome de Down, Pontificia Universidad Católica de Chile, Santiago, Chile

    Francisco Bozinovic & Nibaldo C. Inestrosa

  8. Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia

    Nibaldo C. Inestrosa

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  1. Daniela S. Rivera
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  2. Carolina B. Lindsay
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  3. Juan F. Codocedo
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  4. Laura E. Carreño
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  5. Daniel Cabrera
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  6. Marco A. Arrese
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  7. Carlos P. Vio
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  8. Francisco Bozinovic
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  9. Nibaldo C. Inestrosa
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Correspondence to Daniela S. Rivera or Nibaldo C. Inestrosa.

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Housing, treatment and euthanasia of animals met the guidelines set by the National Institutes of Health (NIH, Baltimore, MD, USA). All experimental procedures involving animals were approved by the Bioethical and Biosafety Committee of the Faculty of Biological Sciences of the Pontificia Universidad Católica de Chile (CBB-121-2013). All efforts were made to minimize animal suffering and to reduce the number of animals used.

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The authors declare that they have no conflict of interest.

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Rivera, D.S., Lindsay, C.B., Codocedo, J.F. et al. Long-Term, Fructose-Induced Metabolic Syndrome-Like Condition Is Associated with Higher Metabolism, Reduced Synaptic Plasticity and Cognitive Impairment in Octodon degus. Mol Neurobiol 55, 9169–9187 (2018). https://doi.org/10.1007/s12035-018-0969-0

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