title: MCT2 expression and lactate influx in anorexigenic and orexigenic neurons of the arcuate nucleus.
abstract: Hypothalamic neurons of the arcuate nucleus control food intake, releasing orexigenic and anorexigenic neuropeptides in response to changes in glucose concentration. Several studies have suggested that the glucosensing mechanism is governed by a metabolic interaction between neurons and glial cells via lactate flux through monocarboxylate transporters (MCTs). Hypothalamic glial cells (tanycytes) release lactate through MCT1 and MCT4; however, similar analyses in neuroendocrine neurons have yet to be undertaken. Using primary rat hypothalamic cell cultures and fluorimetric assays, lactate incorporation was detected. Furthermore, the expression and function of MCT2 was demonstrated in the hypothalamic neuronal cell line, GT1-7, using kinetic and inhibition assays. Moreover, MCT2 expression and localization in the Sprague Dawley rat hypothalamus was analyzed using RT-PCR, in situ hybridization and Western blot analyses. Confocal immunohistochemistry analyses revealed MCT2 localization in neuronal but not glial cells. Moreover, MCT2 was localized to ∼90% of orexigenic and ~60% of anorexigenic neurons as determined by immunolocalization analysis of AgRP and POMC with MCT2-positives neurons. Thus, MCT2 distribution coupled with lactate uptake by hypothalamic neurons suggests that hypothalamic neurons control food intake using lactate to reflect changes in glucose levels.
authors: Laboratorio de Biología Celular, Departamento de Biología Celular, Universidad de Concepción, Concepción, Chile.
authors: Christian
authors: C
authors: Cortes-Campos
authors: Roberto
authors: R
authors: Elizondo
authors: Claudio
authors: C
authors: Carril
authors: Fernando
authors: F
authors: Martínez
authors: Katica
authors: K
authors: Boric
authors: Francisco
authors: F
authors: Nualart
authors: Maria Angeles
authors: MA
authors: Garcia-Robles
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D000855:Anorexia / Q000378:metabolism* / Q000473:pathology; D001111:Arcuate Nucleus of Hypothalamus / Q000473:pathology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D019344:Lactic Acid; D008297:Male; D051379:Mice; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054369:Agouti-Related Protein; D047908:Intracellular Signaling Peptides and Proteins; D027501:Monocarboxylic Acid Transporters; D009479:Neuropeptides; D000068797:Orexins; C490426:Slc16a7 protein, mouse; C091633:Slc16a7 protein, rat; D019344:Lactic Acid; D011333:Pro-Opiomelanocortin
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