Extended Data Fig. 10: Conceptual diagram of this study.

a. Tanycytes secrete EVs in a diurnal manner, with EV release rising toward the onset of the rest/sleep phase over the 24-hour cycle. This increase reflects the cumulative effects of multiple meals during the 12-hour active phase. EV levels remain elevated during the early and middle portions of the rest/sleep phase and are further amplified by circadian clock mechanisms, before declining as the vesicles are gradually taken up and cleared. b. A subset of EVs released by these tanycytes display ppIns on their surface, enabling selective recognition and uptake by IR-positive neurons in the adjacent mediobasal hypothalamus. Through this mechanism, these EVs deliver cargos such as mTORC component(s) to target neurons, thereby sustaining mTORC-dependent satiety signaling during the rest/sleep phase, when anorexigenic hormones such as insulin are low. Taken together, in contrast to hormones such as insulin, which act over short time windows (2–3 hours), this EV-based mechanism provides a 12-hour mode of regulating satiety, offering a new and critical perspective on the control of body weight and metabolic balance. Graphics in this figure were generated through BioRender software with institution purchased license.