Hippocampal lipoprotein lipase regulates energy balance in rodents

Alexandre Picard, Claude Rouch, Nadim Kassis, Valentine S. Moullé, Sophie Croizier, Raphaël G. Denis, Julien Castel, Nicolas Coant, Kathryn Davis, Deborah J. Clegg, Stephen C. Benoit, Vincent Prévot, Sébastien Bouret, Serge Luquet, Hervé Le Stunff, Céline Cruciani-Guglielmacci, Christophe Magnan

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Brain lipid sensing is necessary to regulate energy balance. Lipoprotein lipase (LPL) may play a role in this process. We tested if hippocampal LPL regulated energy homeostasis in rodents by specifically attenuating LPL activity in the hippocampus of rats and mice, either by infusing a pharmacological inhibitor (tyloxapol), or using a genetic approach (adeno-associated virus expressing Cre-GFP injected into Lpllox/lox mice). Decreased LPL activity by either method led to increased body weight gain due to decreased locomotor activity and energy expenditure, concomitant with increased parasympathetic tone (unchanged food intake). Decreased LPL activity in both models was associated with increased de novo ceramide synthesis and neurogenesis in the hippocampus, while intrahippocampal infusion of de novo ceramide synthesis inhibitor myriocin completely prevented body weight gain. We conclude that hippocampal lipid sensing might represent a core mechanism for energy homeostasis regulation through de novo ceramide synthesis.

Original languageEnglish (US)
Pages (from-to)167-176
Number of pages10
JournalMolecular Metabolism
Volume3
Issue number2
DOIs
StatePublished - Apr 2014

Keywords

  • Ceramides
  • Energy expenditure
  • Lipid sensing
  • Obesity
  • Parasympathetic nervous system

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Picard, A., Rouch, C., Kassis, N., Moullé, V. S., Croizier, S., Denis, R. G., Castel, J., Coant, N., Davis, K., Clegg, D. J., Benoit, S. C., Prévot, V., Bouret, S., Luquet, S., Le Stunff, H., Cruciani-Guglielmacci, C., & Magnan, C. (2014). Hippocampal lipoprotein lipase regulates energy balance in rodents. Molecular Metabolism, 3(2), 167-176. https://doi.org/10.1016/j.molmet.2013.11.002