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Updated: Mar 7, 2026

Characterization of Adipocyte-Derived Extracellular Vesicle Secretion Using a CD63-GFP Reporter Mouse Model In Vivo and In Vitro
Published on: December 5, 2025
Metabolic regulation by tanycyte-derived extracellular vesicles through insulin precursor-mediated neuronal
Yuna Choi1, Min Woo Kim1, Gyeongyun Go1
1Department of Molecular Pharmacology Einstein Institute of Neuroimmunology and Inflammation Albert Einstein College of Medicine, Bronx, NY, USA.
Abstract:
The hypothalamus regulates feeding and metabolic balance in response to metabolic cues. Here we report that extracellular vesicles (EVs) are secreted from the mediobasal hypothalamus in a diurnal manner that is influenced by daily feeding. Sox2-positive tanycytes have a critical role in maintaining the diurnal pattern of hypothalamic EV release. Inhibition of tanycyte EV release leads to a loss of feeding diurnality, weight control and blood glucose homoeostasis, whereas supplementation with tanycytic EVs confers metabolic benefits. We show that a subset of tanycytic EVs carries surface prepro-insulin (ppIns), which mediates recognition and uptake by insulin-receptor-positive hypothalamic neurons. These EVs are loaded with mTORC components, including Rictor in a low-phosphorylation state, and support hypothalamic neuronal signalling. Both ppIns and Rictor are important for the EV-mediated preservation of feeding rhythmicity and resistance to diet-induced metabolic dysfunction. Collectively, these findings identify tanycyte-derived EVs as regulators of feeding diurnality through insulin precursor-directed targeting and delivery of mTORC components to hypothalamic neurons.
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