Abstract

Introduction- Hypothalamic tanycytes are localized in the lower lateral wall of the third ventricle. They are in contact with CSF and have extended cell processes that contact feeding-controlling neurons in the arcuate nucleus (AN), NPY- and POMC-expressing neurons. Previously, we demonstrated that tanycytes in culture release lactate in response to high glucose, which reach hypothalamic neurons through MCTs transporters. Our hypothesis is that tanycytes communicates with the AN-neurons not only through lactate but also by ketone bodies in fasting. Here we study the ketogenic potential of tanycytes and the POMC-neurons activity in response to lactate and β-HB. Methods- We made colorimetric assays to measure the release of β-HB from tanyctes. Trough whole cell-patch clamp we evaluate changes in action potential frequency (APF) of POMC-EGFP neurons in response to lactate and β-HB. Furthermore, we made qPCR in hypothalamic neurons to evaluate POMC and NPY expression in response to lactate and β-HB. Results- Tanycytes release up 20 μM of β-HB, which is enhanced by AMPK activation. POMC-EGFP neurons respond to glucose and lactate, increasing the APF, but they seem to be inhibited in the presence of β-HB. Interestingly, by incubating the slices with 4-cinnamate, a blocker of MCT1/4, POMC-neurons do not respond to glucose. Similarly, in these neurons lactate and β-HB have opposite effects on POMC and NPY expression. Discussion-These results agree with the hypothesis that in POMC neurons, an indirect mechanism of glucodetection operates. Thus, lactate activates POMC-neurons and β-HB inhibits them, presumably through HCA2. Acknowledge- FONDECYT 1180871