title: Hippocampal lipoprotein lipase regulates energy balance in rodents.
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 Lpl (lox/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.
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA, EAC 4413 CNRS, Case courrier 7126, 4, rue Marie Andrée Lagroua Weill-Hallé, F-75205 Paris Cedex 13, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Picard
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA, EAC 4413 CNRS, Case courrier 7126, 4, rue Marie Andrée Lagroua Weill-Hallé, F-75205 Paris Cedex 13, France ; Centre National de la Recherche Scientifique-CNRS EAC 4413, F-75205 Paris, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Rouch
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA, EAC 4413 CNRS, Case courrier 7126, 4, rue Marie Andrée Lagroua Weill-Hallé, F-75205 Paris Cedex 13, France ; Centre National de la Recherche Scientifique-CNRS EAC 4413, F-75205 Paris, France.
authors.forename: Nadim
authors.initials: N
authors.lastname: Kassis
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA, EAC 4413 CNRS, Case courrier 7126, 4, rue Marie Andrée Lagroua Weill-Hallé, F-75205 Paris Cedex 13, France.
authors.forename: Valentine S
authors.initials: VS
authors.lastname: Moullé
authors.affiliation: Jean-Pierre Aubert Research Center, Development and Plasticity of the Postnatal Brain, INSERM U837, 59045 Lille Cedex, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Croizier
authors.affiliation: Jean-Pierre Aubert Research Center, Development and Plasticity of the Postnatal Brain, INSERM U837, 59045 Lille Cedex, France.
authors.forename: Raphaël G
authors.initials: RG
authors.lastname: Denis
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA, EAC 4413 CNRS, Case courrier 7126, 4, rue Marie Andrée Lagroua Weill-Hallé, F-75205 Paris Cedex 13, France ; Centre National de la Recherche Scientifique-CNRS EAC 4413, F-75205 Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Castel
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA, EAC 4413 CNRS, Case courrier 7126, 4, rue Marie Andrée Lagroua Weill-Hallé, F-75205 Paris Cedex 13, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Coant
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Davis
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Clegg
authors.affiliation: Department of Psychiatry, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Benoit
authors.affiliation: Jean-Pierre Aubert Research Center, Development and Plasticity of the Postnatal Brain, INSERM U837, 59045 Lille Cedex, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Prévot
authors.affiliation: Jean-Pierre Aubert Research Center, Development and Plasticity of the Postnatal Brain, INSERM U837, 59045 Lille Cedex, France ; The Saban Research Institute, Neuroscience Program, Children's Hospital Los Angeles, University of Southern California, Los Angeles, USA.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Bouret
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA, EAC 4413 CNRS, Case courrier 7126, 4, rue Marie Andrée Lagroua Weill-Hallé, F-75205 Paris Cedex 13, France ; Centre National de la Recherche Scientifique-CNRS EAC 4413, F-75205 Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Luquet
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA, EAC 4413 CNRS, Case courrier 7126, 4, rue Marie Andrée Lagroua Weill-Hallé, F-75205 Paris Cedex 13, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Stunff
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA, EAC 4413 CNRS, Case courrier 7126, 4, rue Marie Andrée Lagroua Weill-Hallé, F-75205 Paris Cedex 13, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Cruciani-Guglielmacci
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA, EAC 4413 CNRS, Case courrier 7126, 4, rue Marie Andrée Lagroua Weill-Hallé, F-75205 Paris Cedex 13, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Magnan
keywords: AAV, adeno-associated virus; ANS, autonomic nervous system; CERS, ceramide synthase; CNS, central nervous system; Ceramides; Energy expenditure; GFP, green fluorescent protein; LPL, lipoprotein lipase; Lipid sensing; Obesity; Parasympathetic nervous system; RQ, respiratory quotient; SMPD1, acid sphingomyelin phosphodiesterase 1; SPHK1, sphingosine kinase 1; SPT, serine palmitoyltransferase; TG, triglycerides