Peroxisome proliferator-activated receptor gamma-coactivator-1 alpha coordinates sphingolipid metabolism, lipid raft composition and myelin protein synthesis

Authors

  • Alberto Camacho,

    1. Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
    Current affiliation:
    1. Department of Biochemistry, Faculty of Medicine, Center for Research and Development in Health Sciences, Madero y Dr. Aguirre Pequeño Col. Mitras Centro S/N. Monterrey, N.L., México
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  • Jeffrey K. Huang,

    1. Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Veterinary Medicine, Cambridge, UK
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  • Ilse Delint-Ramirez,

    1. Department of Pharmacology, Faculty of Medicine, Autonomous University of Nuevo León, Monterrey, Mexico
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  • Chong Yew Tan,

    1. Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
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  • Maria Fuller,

    1. Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, SA, Australia
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  • Christopher J. Lelliott,

    1. Department of Biosciences, AstraZeneca R&D, Mölndal, Sweden
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  • Antonio Vidal-Puig,

    1. Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
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  • Robin J. M. Franklin

    Corresponding author
    1. Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Veterinary Medicine, Cambridge, UK
    • Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
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Correspondence: Prof. Robin J. M. Franklin, as above.

E-mail: rjf1000@cam.ac.uk

Abstract

Peroxisome proliferator-activated receptor gamma-coactivator-1 alpha (PGC1a) is involved in energy and lipid metabolism, and its loss leads to neurodegenerative changes in the striatum. Here we performed lipidomic analysis on brain extracts from PGC1a mutant and wild-type mice. We found increased phosphatidylcholine and decreased ceramides in the brain of PGC1a-deficient mice. An analysis of lipid raft fractions revealed increased ceramide, glucocylceramides and GM1 ganglioside in the PGC1a mutants. In the cerebellum, we observed a decrease in proteins associated with myelination, but were unable to detect any morphological abnormalities in compact myelin formation in PGC1a mutants compared with wild-type mice. Although PGC1a is involved in lipid biosynthesis, we concluded that altered lipid composition in the PGC1a mutant did not directly affect central nervous system myelin morphology.

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