title: Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization through Glycolysis.
abstract: The Wnt signaling pathway is critical for a number of functions in the central nervous system, including regulation of the synaptic cleft structure and neuroprotection against injury. Deregulation of Wnt signaling has been associated with several brain pathologies, including Alzheimer's disease. In recent years, it has been suggested that the Wnt pathway might act as a central integrator of metabolic signals from peripheral organs to the brain, which would represent a new role for Wnt signaling in cell metabolism. Energy metabolism is critical for normal neuronal function, which mainly depends on glucose utilization. Brain energy metabolism is important in almost all neurological disorders, to which a decrease in the capacity of the brain to utilize glucose has been linked. However, little is known about the relationship between Wnt signaling and neuronal glucose metabolism in the cellular context. In the present study, we found that acute treatment with the Wnt3a ligand induced a large increase in glucose uptake, without changes in the expression or localization of glucose transporter type 3. In addition, we observed that Wnt3a treatment increased the activation of the metabolic sensor Akt. Moreover, we observed an increase in the activity of hexokinase and in the glycolytic rate, and both processes were dependent on activation of the Akt pathway. Furthermore, we did not observe changes in the activity of glucose-6-phosphate dehydrogenase or in the pentose phosphate pathway. The effect of Wnt3a was independent of both the transcription of Wnt target genes and synaptic effects of Wnt3a. Together, our results suggest that Wnt signaling stimulates glucose utilization in cortical neurons through glycolysis to satisfy the high energy demand of these cells.
authors.affiliation: From the Centro de Envejecimiento y Regeneración (CARE-UC), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile.|the Universidad de Atacama, Facultad de Ciencias Naturales, Departamento de Química y Biología, Copayapu 485, Copiapó, Chile.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cisternas
authors.affiliation: From the Centro de Envejecimiento y Regeneración (CARE-UC), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile.
authors.forename: Paulina
authors.initials: P
authors.lastname: Salazar
authors.affiliation: From the Centro de Envejecimiento y Regeneración (CARE-UC), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile.
authors.forename: Carmen
authors.initials: C
authors.lastname: Silva-Álvarez
authors.affiliation: the Centro de Estudios Científicos (CECs), Casilla 1469, Valdivia, Chile.
authors.forename: L Felipe
authors.initials: LF
authors.lastname: Barros
authors.affiliation: From the Centro de Envejecimiento y Regeneración (CARE-UC), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile, ninestrosa@bio.puc.cl.|the Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney 1235, Australia, and.|the Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas 6200732, Chile.
authors.forename: Nibaldo C
authors.initials: NC
authors.lastname: Inestrosa
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D060509:Wnt3A Protein / Q000378:metabolism
chemical_list: D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D005954:Glucosephosphate Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt
keywords: Wnt signaling; energy metabolism; glucose; glucose metabolism; glycolysis