Monocarboxylate Transporters (MCTs) and their Role in Hypothalamic Glucosensing

Abstract

Monocarboxylate transporters (MCTs) are a family of transporters, which participate in the facilitated diffusion of lactate as well as the incorporation and release of several other metabolically important monocarboxylates, such as Pyruvate and ketone bodies. It has been established that lactate and ketone bodies have a role in energy balance. In the brain, lactate is an important oxidative energy substrate, and its intracerebroventricular (ICV) administration decreases food intake in rats. An opposite effect is produced by the ketone bodies. Several studies have suggested that the glucosensing mechanism is governed by a metabolic interaction between neurons and glial cells via lactate flux through MCTs. Hypothalamic glial cells (tanycytes) release lactate through MCT1 and MCT4. Moreover, orexigenic and anorexigenic neurons of the arcuate nucleus (AN) have high membrane immunoreactivity for MCT2, which is involved in lactate influx, suggesting that tanycytes indirectly control neuronal activity via glucose. This review will focus on MCT expression in the hypothalamus, a master regulation center for glucose homeostasis, and the evidence for a metabolic interaction between tanycytes and neuroendocrine neurons using monocarboxylates.