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Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding

Molecular Psychiatry volume 19, pages 1095–1105 (2014)Cite this article

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Abstract

Circulating triglycerides (TGs) normally increase after a meal but are altered in pathophysiological conditions, such as obesity. Although TG metabolism in the brain remains poorly understood, several brain structures express enzymes that process TG-enriched particles, including mesolimbic structures. For this reason, and because consumption of high-fat diet alters dopamine signaling, we tested the hypothesis that TG might directly target mesolimbic reward circuits to control reward-seeking behaviors. We found that the delivery of small amounts of TG to the brain through the carotid artery rapidly reduced both spontaneous and amphetamine-induced locomotion, abolished preference for palatable food and reduced the motivation to engage in food-seeking behavior. Conversely, targeted disruption of the TG-hydrolyzing enzyme lipoprotein lipase specifically in the nucleus accumbens increased palatable food preference and food-seeking behavior. Finally, prolonged TG perfusion resulted in a return to normal palatable food preference despite continued locomotor suppression, suggesting that adaptive mechanisms occur. These findings reveal new mechanisms by which dietary fat may alter mesolimbic circuit function and reward seeking.

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Acknowledgements

This work was supported by young investigator ATIP grant from the Centre National la Recherche Scientifique (CNRS), a grant from the Région Île-de-France, from the University Paris Diderot-Paris 7, from the ‘Agence Nationale de la Recherche’ ANR-09-BLAN-0267-02 and ANR 11 BSV1 021 01. CC received a PhD fellowship from the CNRS and a research grant from the Société Francophone du Diabète-Roche (SFD). TSH was supported by an NIH Grant DA026504 and a scientist exchange award from the University of Paris Diderot-Paris VII. We express our gratitude to Aundrea Rainwater for help in establishing the infusion technique and operant schedule and to Dr Susanna Hofmann for critical review of the manuscript. We acknowledge the technical platform Functional and Physiological Exploration Platform (FPE) and the platform ‘Bioprofiler’ of the Unit ‘Biologie Fonctionnelle et Adaptative’, (University Paris Diderot, Sorbonne Paris Cité, BFA, UMR 8251 CNRS, F-75205 Paris, France) for metabolic and behavioral analysis and for the provision of high-performance liquid chromatography data. We also acknowledge the animal core facility ‘Buffon’ of the University Paris Diderot Paris 7/Institut Jacques Monod, Paris for animal husbandry and breeding, together with Dr Serban Morosan, for its precious help with regard to DIO mice. We thank Mrs Olja Kacanski for administrative support, Mr Karim Sahabi for engineering support, Mrs Gaëlle Charlon, Mrs Sandrine Olivré and Mr Ludovic Maingault for care of animals.

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Authors and Affiliations

  1. Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, Paris, France,

    C Cansell, J Castel, R G P Denis, C Rouch, A-S Delbes, S Martinez, C Magnan & S Luquet

  2. Institut Jacques Monod, Sorbonne Paris Cité, Université Paris Diderot, Paris, France,

    D Mestivier

  3. Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health, München/Neuherberg, Germany

    B Finan & M H Tschöp

  4. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    J G Maldonado-Aviles & R J DiLeone

  5. Department of Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands

    M Rijnsburger & S E la Fleur

  6. Division of Metabolic Diseases, Department of Medicine, Technische Universität München, München, Germany,

    M H Tschöp

  7. Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    R H Eckel

  8. Department of Neurosciences, University of California, La Jolla, CA, USA

    T S Hnasko

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  1. C Cansell
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Cansell, C., Castel, J., Denis, R. et al. Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding. Mol Psychiatry 19, 1095–1105 (2014). https://doi.org/10.1038/mp.2014.31

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