title: Imaging liver and brain glycogen metabolism at the nanometer scale.
abstract: In mammals, glycogen synthesis and degradation are dynamic processes regulating blood and cerebral glucose-levels within a well-defined physiological range. Despite the essential role of glycogen in hepatic and cerebral metabolism, its spatiotemporal distribution at the molecular and cellular level is unclear. By correlating electron microscopy and ultra-high resolution ion microprobe (NanoSIMS) imaging of tissue from fasted mice injected with (13)C-labeled glucose, we demonstrate that liver glycogenesis initiates in the hepatocyte perinuclear region before spreading toward the cell membrane. In the mouse brain, we observe that (13)C is inhomogeneously incorporated into astrocytic glycogen at a rate ~25 times slower than in the liver, in agreement with prior bulk studies. This experiment, using temporally resolved, nanometer-scale imaging of glycogen synthesis and degradation, provides greater insight into glucose metabolism in mammalian organs and shows how this technique can be used to explore biochemical pathways in healthy and diseased states.
authors.affiliation: Laboratory for Biological Geochemistry, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Institute of Physics of Biological Systems, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. Electronic address: yuhei.takado@epfl.ch.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Takado
authors.affiliation: Centre Interdisciplinaire de Microscopie Electronique, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Graham
authors.initials: G
authors.lastname: Knott
authors.affiliation: Electron Microscopy Facility, Université de Lausanne, Lausanne, Switzerland.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Humbel
authors.affiliation: Laboratory for Biological Geochemistry, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Escrig
authors.affiliation: Nestlé Institute of Health Science, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Masoodi
authors.affiliation: Laboratory for Biological Geochemistry, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Center for Advanced Surface Analysis, Institute of Earth Sciences, University of Lausanne, Lausanne, Switzerland. Electronic address: anders.meibom@epfl.ch.
authors.forename: Anders
authors.initials: A
authors.lastname: Meibom
authors.affiliation: Institute of Physics of Biological Systems, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. Electronic address: arnaud.comment@epfl.ch.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Comment
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001786:Blood Glucose / Q000737:chemistry; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002247:Carbon Isotopes / Q000737:chemistry; D003600:Cytosol / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D036103:Nanotechnology / Q000379:methods*
chemical_list: D001786:Blood Glucose; D002247:Carbon Isotopes; D006003:Glycogen; D005947:Glucose
keywords: Astrocytes; Carbon-13; Glucose metabolism; Hepatocytes; NanoSIMS