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.
Highlights
Neurons within the arcuate nucleus (AN) of the hypothalamus are capable of responding to changes in glucose and lactate concentrations [1,2]
Several neuronal populations capable of responding to changes in glucose concentration are located within the AN
These neurons couple the fluctuations in blood glucose levels with a complex network of neurochemical and neurophysiologic responses that control food intake and feeding behavior [3]
Summary
Neurons within the arcuate nucleus (AN) of the hypothalamus are capable of responding to changes in glucose and lactate concentrations [1,2]. These neurons couple blood glucose fluctuations with a complex network of neurochemical and neurophysiologic responses that control energy expenditure and feeding behavior [3]. On the other hand one population within the hypothalamus, glucose-exited neurons (GE), increases its firing rate in response to elevated glucose levels. Alternative, neurons that reduced their firing rate in response to increased glucose levels are known as glucose-inhibited neurons (GI) [5,6]. It has been proposed that POMC neurons could be correspond to GE neurons [8,9]
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