El transporte de la glucosa en las células gliales del cerebro obeso

Gabriel López-Ramírez, Orquidia G Méndez-Flores

Resumen


La pandemia de enfermedades metabólicas, asociada a la transición nutricional reciente y al estilo de vida sedentario, afecta la salud del individuo y modifica la funcionalidad del cerebro. La inflamación de bajo grado generalizada (desregulación inmunológica crónica y sistémica, asociada al tejido adiposo) durante las afecciones metabólicas desencadena neurodegeneración, envejecimiento del cerebro y deterioro cognitivo. Estos cambios funcionales están correlacionados con una tasa metabólica baja, con pérdida neuronal y con una gliosis reactiva. El objetivo del presente trabajo fue condensar y analizar la información relacionada con la participación del transporte de glucosa de las estirpes gliales, durante el mantenimiento de la homeostasis metabólica en el cerebro obeso. Para este fin, revisamos la base de datos PubMed y reunimos la información más reciente al respecto. Concluimos que las citocinas pro-inflamatorias y los mediadores químicos de la alimentación intervienen en la modulación de los principales transportadores de glucosa (GLUT1-GLUT5) en las células gliales del cerebro, además de que se relacionan con la disminución en la expresión del transportador mayoritario de la barrera hematoencefálica, GLUT1, y la condición de inanición en el cerebro. Los mecanismos moleculares implicados en la obesidad comparten un gran parecido con los cambios metabólicos en sobrepeso y en condiciones de malnutrición por exceso. Estas desregulaciones tempranas están vinculadas a la tasa metabólica baja del encéfalo, la neurodegeneración y también puede explicar los cambios identificados en el comportamiento y en la cognición, los cuales prevalecen en un cerebro obeso.

Abstract

The pandemic of metabolic diseases, associated with the recent nutritional transition and sedentary lifestyle, affects the health of the individual and modifies the functionality of the brain. Widespread low-grade inflammation (chronic and systemic immune dysregulation, associated with adipose tissue) during metabolic conditions triggers neurodegeneration, brain aging, and cognitive decline. These functional changes are correlated with low metabolic rate, neuronal loss, and reactive gliosis. The objective of the present work was to condense and analyze the information regarding the participation of glucose transport of glial lineages, during the maintenance of metabolic homeostasis in the obese brain. For this purpose, we reviewed the PubMed database and gathered the most recent information on it. We conclude that pro-inflammatory cytokines and chemical mediators of food are involved in the modulation of the main glucose transporters (GLUT1-GLUT5) in the glial cells of the brain, in addition to being related to the decrease in the expression of the main transporter of the blood-brain barrier, GLUT1, and the starvation condition in the brain. The molecular mechanisms involved in obesity share a great resemblance to the metabolic changes in overweight and under conditions of excess malnutrition. These early dysregulations are linked to the brain's low metabolic rate, neurodegeneration, and may also explain the identified changes in behavior and cognition that are associated with the obese brain.

Keywords: glucose transport; obesity; metabolism; glial cells.


Palabras clave


Transporte de glucosa; obesidad; metabolismo; células gliales.

Texto completo:

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Referencias


Rivera JA, Barquera S, González-Cossío T, Olaiz G, Sepúlveda J. Nutrition Transition in Mexico and in Other Latin American Countries. Nutr Rev. 2004;62:S149-S157. doi:10.1111/j.1753-4887.2004.tb00086.x

Ortega MA, Fraile-Martínez Ó, García-Montero C, Alvarez-Mon MA, Lahera G, Monserrat J, Llavero-Valero M, Mora F, Rodríguez-Jiménez R, Fernandez-Rojo S, Quintero J, Alvarez De Mon M. Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection. Front Nutr. 2022;9:867150. doi:10.3389/fnut.2022.867150

Ríos-Hoyo A, Cortés MJ, Ríos-Ontiveros H, Meaney E, Ceballos G, Gutiérrez-Salmeán G. Obesity, Metabolic Syndrome, and Dietary Therapeutical Approaches with a Special Focus on Nutraceuticals (Polyphenols): A Mini-Review. Int J Vitam Nutr Res. 2014;84(3-4):113-123. doi:10.1024/0300-9831/a000198

Kwok KO, Fries LR, Silva-Zolezzi I, Thakkar SK, Iroz A, Blanchard C. Effects of Probiotic Intervention on Markers of Inflammation and Health Outcomes in Women of Reproductive Age and Their Children. Front Nutr. 2022;9:889040. doi:10.3389/fnut.2022.889040

Gómez-Dantés O, Alonso-Concheiro A, Razo-García C, Lilia Bravo-Ruiz M, Orozco E, Serván-Mori E, Alpuche-Aranda C, Hernández-Ávila M, Híjar-Medina M, Lamadrid-Figueroa H, Medina-Mora ME, Mohar-Betancourt A, Reynales-Shigematsu LM, Rivera-Dommarco J, Riojas-Rodríguez H, Campillo-García JI, Lozano-Ascencio R, Martínez-Palomo A. Prioridades de Investigación En Salud En México. 1a. Cuernavaca, Morelos, México: Instituto Nacional de Salud Pública; 2017.

Henn RE, Noureldein MH, Elzinga SE, Kim B, Savelieff MG, Feldman EL. Glial-neuron crosstalk in health and disease: A focus on metabolism, obesity, and cognitive impairment. Neurobiol Dis. 2022;170:105766. doi:10.1016/j.nbd.2022.105766

Robb JL, Morrissey NA, Weightman Potter PG, Smithers HE, Beall C, Ellacott KLJ. Immunometabolic Changes in Glia – A Potential Role in the Pathophysiology of Obesity and Diabetes. Neuroscience. 2020;447:167-181. doi:https://doi.org/10.1016/j.neuroscience.2019.10.021

Marelli C, Salsano E, Politi LS, Labauge P. Spinal cord involvement in adult-onset metabolic and genetic diseases. J Neurol Neurosurg Psychiatry. 2019;90(2):211 LP - 218. doi:10.1136/jnnp-2018-318666

World Health Organization [WHO]. Obesity.

World Health Organization [WHO]. ICD-11 for Mortality and Morbidity Statistics (Version: 02/2022). Online. https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/1890900469. Published 2022. Accessed July 8, 2022.

Lampe L, Zhang R, Beyer F, Huhn S, Kharabian Masouleh S, Preusser S, Bazin PL, Schroeter ML, Villringer A, Witte AV. Visceral obesity relates to deep white matter hyperintensities via inflammation. Ann Neurol. 2019;85(2):194-203. doi:10.1002/ana.25396

Monteiro R, Sivasubramanian MK, Balasubramanian P, Subramanian M. Obesity-Induced Sympathoexcitation is Associated with Glial Senescence in the Brainstem. FASEB J. 2020;34(S1):1. doi:https://doi.org/10.1096/fasebj.2020.34.s1.06223

Balasubramanian P, Branen L, Sivasubramanian MK, Monteiro R, Subramanian M. Aging is associated with glial senescence in the brainstem - implications for age-related sympathetic overactivity. Aging (Albany NY). 2021;13(10):13460-13473. doi:10.18632/aging.203111

Salas-Venegas V, Flores-Torres RP, Rodríguez-Cortés YM, Rodríguez-Retana D, Ramírez-Carreto RJ, Concepción-Carrillo LE, Pérez-Flores LJ, Alarcón-Aguilar A, López-Díazguerrero NE, Gómez-González B, Chavarría A, Konigsberg M. The Obese Brain: Mechanisms of Systemic and Local Inflammation, and Interventions to Reverse the Cognitive Deficit. Front Integr Neurosci. 2022;16. doi:10.3389/fnint.2022.798995

Gómez-Apo E, Mondragón-Maya A, Ferrari-Díaz M, Silva-Pereyra J. Structural Brain Changes Associated with Overweight and Obesity. J Obes. 2021;2021:6613385. doi:10.1155/2021/6613385

Milte CM, Ball K, Crawford D, McNaughton SA. Diet quality and cognitive function in mid-aged and older men and women. BMC Geriatr. 2019;19(1):361. doi:10.1186/s12877-019-1326-5

Douglass JD, Dorfman MD, Thaler JP. Glia: silent partners in energy homeostasis and obesity pathogenesis. Diabetologia. 2017;60(2):226-236. doi:10.1007/s00125-016-4181-3

Zulfiqar S, Garg P, Nieweg K. Contribution of astrocytes to metabolic dysfunction in the Alzheimer’s disease brain. Biol Chem. 2019;400(9):1113-1127. doi:10.1515/hsz-2019-0140

Hao S, Dey A, Yu X, Stranahan AM. Dietary obesity reversibly induces synaptic stripping by microglia and impairs hippocampal plasticity. Brain Behav Immun. 2016;51:230-239. doi:10.1016/j.bbi.2015.08.023

Cope EC, LaMarca EA, Monari PK, Olson LB, Martinez S, Zych AD, Katchur NJ, Gould E. Microglia Play an Active Role in Obesity-Associated Cognitive Decline. J Neurosci. 2018;38(41):8889-8904. doi:10.1523/JNEUROSCI.0789-18.2018

Sobesky JL, Barrientos RM, De May HS, Thompson BM, Weber MD, Watkins LR, Maier SF.. High-fat diet consumption disrupts memory and primes elevations in hippocampal IL-1β, an effect that can be prevented with dietary reversal or IL-1 receptor antagonism. Brain Behav Immun. 2014;42:22-32. doi:10.1016/j.bbi.2014.06.017

Fujita Y, Yamashita T. The Effects of Leptin on Glial Cells in Neurological Diseases. Front Neurosci. 2019;13:828. doi:10.3389/fnins.2019.00828

Rahman MH, Kim M-S, Lee I-K, Yu R, Suk K. Interglial Crosstalk in Obesity-Induced Hypothalamic Inflammation. Front Neurosci. 2018;12:939. doi:10.3389/fnins.2018.00939

Zhao F-Q, Keating AF. Functional properties and genomics of glucose transporters. Curr Genomics. 2007;8(2):113-128. doi:10.2174/138920207780368187

Wilson-O’Brien AL, Patron N, Rogers S. Evolutionary ancestry and novel functions of the mammalian glucose transporter (GLUT) family. BMC Evol Biol. 2010;10:152. doi:10.1186/1471-2148-10-152

Yu S, Ding WG. The 45 kDa form of glucose transporter 1 (GLUT1) is localized in oligodendrocyte and astrocyte but not in microglia in the rat brain. Brain Res. 1998;797(1):65-72. doi:10.1016/s0006-8993(98)00372-2

Vannucci SJ, Maher F, Simpson IA. Glucose transporter proteins in brain: Delivery of glucose to neurons and glia. Glia. 1997;21(1):2-21. doi:10.1002/(SICI)1098-1136(199709)21:1<2::AID-GLIA2>3.0.CO;2-C

Horikoshi Y, Sasaki A, Taguchi N, Maeda M, Tsukagoshi H, Sato K, Yamaguchi H. Human GLUT5 immunolabeling is useful for evaluating microglial status in neuropathological study using paraffin sections. Acta Neuropathol. 2003;105(2):157-162. doi:10.1007/s00401-002-0627-4

Mizuno TM, Lew PS, Jhanji G. Regulation of the Fructose Transporter Gene Slc2a5 Expression by Glucose in Cultured Microglial Cells. Int J Mol Sci. 2021;22(23). doi:10.3390/ijms222312668

Jurcovicova J. Glucose transport in brain - effect of inflammation. Endocr Regul. 2014;48(1):35-48. doi:10.4149/endo_2014_01_35

Hendrix RD, Ou Y, Davis JE, Odle AK, Groves TR, Allen AR, Childs G V, Barger SW. Alzheimer amyloid-β- peptide disrupts membrane localization of glucose transporter 1 in astrocytes: implications for glucose levels in brain and blood. Neurobiol Aging. 2021;97:73-88. doi:10.1016/j.neurobiolaging.2020.10.001

Fuente-Martín E, García-Cáceres C, Granado M, de Ceballos ML, Sánchez-Garrido MÁ, Sarman B, Liu Z-W, Dietrich MO, Tena-Sempere M, Argente-Arizón P, Díaz F, Argente J, Horvath TL, Chowen JA. Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. J Clin Invest. 2012;122(11):3900-3913. doi:10.1172/JCI64102

Tomassoni D, Martinelli I, Moruzzi M, Micioni Di Bonaventura MV, Cifani C, Amenta F, Tayebati SK. Obesity and Age-Related Changes in the Brain of the Zucker Lepr (fa/fa) Rats. Nutrients. 2020;12(5). doi:10.3390/nu12051356

Naranjo V, Contreras A, Merino B, Plaza A, Lorenzo MP, García-Cáceres C, García A, Chowen JA, Ruiz-Gayo M, Del Olmo N, Cano V. Specific Deletion of the Astrocyte Leptin Receptor Induces Changes in Hippocampus Glutamate Metabolism, Synaptic Transmission and Plasticity. Neuroscience. 2020;447:182-190. doi:https://doi.org/10.1016/j.neuroscience.2019.10.005

Fuente-Martín E, García-Cáceres C, Argente-Arizón P, Díaz F, Granado M, Freire-Regatillo A, Castro-González D, Ceballos ML, Frago LM, Dickson SL, Argente J, Chowen JA. Ghrelin Regulates Glucose and Glutamate Transporters in Hypothalamic Astrocytes. Sci Rep. 2016;6(1):23673. doi:10.1038/srep23673

Schüler R, Seebeck N, Osterhoff MA, Witte V, Flöel A, Busjahn A, Jais A, Brüning JC, Frahnow T, Kabisch S, Pivovarova O, Hornemann S, Kruse M, Pfeiffer AFH. VEGF and GLUT1 are highly heritable, inversely correlated and affected by dietary fat intake: Consequences for cognitive function in humans. Mol Metab. 2018;11:129-136. doi:10.1016/j.molmet.2018.02.004

Hernandez-Garzón E, Fernandez AM, Perez-Alvarez A, Genis L, Bascuñana P, Fernandez de la Rosa R, Delgado M, Angel Pozo M, Moreno E, McCormick PJ, Santi A, Trueba-Saiz A, Garcia-Caceres C, Tschöp MH, Araque A, Martin ED, Torres Aleman I. The insulin-like growth factor I receptor regulates glucose transport by astrocytes. Glia. 2016;64(11):1962-1971. doi:10.1002/glia.23035

Sasaki T. Neural and Molecular Mechanisms Involved in Controlling the Quality of Feeding Behavior: Diet Selection and Feeding Patterns. Nutrients. 2017;9(10). doi:10.3390/nu9101151

Gruetter R, Novotny EJ, Boulware SD, Rothman DL, Mason GF, Shulman GI, Shulman RG, Tamborlane WV. Direct measurement of brain glucose concentrations in humans by 13C NMR spectroscopy. Proc Natl Acad Sci USA. 1992;89(3):1109-1112. doi:10.1073/pnas.89.3.1109

Pardridge WM, Triguero D, Farrell CR. Downregulation of blood-brain barrier glucose transporter in experimental diabetes. Diabetes. 1990. doi:10.2337/diab.39.9.1040

Mooradian AD, Chung HC, Shah GN. GLUT-1 expression in the cerebra of patients with Alzheimer’s disease. Neurobiol Aging. 1997;18(5):469-474. doi:10.1016/s0197-4580(97)00111-5




DOI: https://doi.org/10.25009/eb.v13i32.2613

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