Metabolic regulation by tanycyte-derived extracellular vesicles through insulin precursor-mediated neuronal recognition and mTORC component delivery - PubMed
5 days ago
- #hypothalamus
- #extracellular vesicles
- #metabolic regulation
- Hypothalamus regulates feeding and metabolic balance via metabolic cues.
- Extracellular vesicles (EVs) are secreted from the mediobasal hypothalamus in a diurnal pattern influenced by daily feeding.
- Sox2-positive tanycytes play a critical role in maintaining the diurnal pattern of hypothalamic EV release.
- Inhibition of tanycyte EV release disrupts feeding diurnality, weight control, and blood glucose homeostasis.
- Supplementation with tanycytic EVs provides metabolic benefits.
- A subset of tanycytic EVs carries surface prepro-insulin (ppIns), which mediates recognition and uptake by insulin-receptor-positive hypothalamic neurons.
- These EVs contain mTORC components, including low-phosphorylation-state Rictor, supporting hypothalamic neuronal signaling.
- Both ppIns and Rictor are crucial for EV-mediated preservation of feeding rhythmicity and resistance to diet-induced metabolic dysfunction.
- Tanycyte-derived EVs regulate feeding diurnality through insulin precursor-directed targeting and mTORC component delivery to hypothalamic neurons.