Figure 2. Leptin and other circulating signals are transported from the periphery to hypothalamic and extra-hypothalamic areas around the 3V by tanycytes.

(a) Representative photomicrographs with fluorescent leptin (25 nmol/mouse) labelled tanycytic processes (arrows) and cell bodies (arrowheads; white labeling), where fluorescent bioactive leptin was administered intravenously in wild-type mice. (b) Similar experiment using fluorescent point-mutated leptin and showing that the mutated leptin is taken up by tanycytes, but remains blocked at the tanycytic end-feet (asterisk) due to its inability to stimulate LepR-mediated EGFR activation²⁴, as detailed in the schematics (c,d). The cell nuclei are counterstained with Hoechst solution. Adapted with permission from²⁵. (c) Schematic showing tanycytes as the gateway for the passage of leptin and other blood-borne metabolic signals from fenestrated blood vessels to the CSF of the 3V. Tanycytes of the ARH sense CSF-borne molecules transported by tanycytes from the periphery, translate and transmit the information to neurons under the influence of the tanycytic network. (d) Diseased state or the experimental conditions in which mechanisms related to leptin transport^24,25, insulin⁷⁷, ghrelin transport^78,79 or action⁷⁷ are altered in tanycytes. Cx43 gap junction–mediated tanycytic metabolic networks are required for the transport of lactate, produced and released by tanycytes, to glucose-insensitive POMC neurons³⁶. Tanycytes also play a role in the control of daily circadian changes⁹⁶. 3V, third ventricle; ARH, arcuate nucleus of the hypothalamus; Cx43, connexin 43; DIO, diet-induced obesity; Egfr, epidermal growth factor receptor; Insr, insulin receptor; LepR, leptin receptor; Mct, monocarboxylate transporters; POMC, pro-opiomelanocortin; SCN, suprachiasmatic nucleus; TanKO, gene selectively knocked out in tanycytes; TanKD, gene selectively knocked down in tanycytes.