(5) This reveals a dual role for endothelial Notch signaling: it mitigates short-term glucose transport deficits but contributes to central insulin resistance over time. Here, we identify the hypothalamic Notch-Cav1 axis as a therapeutic target for addressing diet-induced metabolic disorders!

(4) However, sustained Notch1 activation suppresses caveolin-1 expression, reduces insulin transport across the BBB and impairs systemic insulin sensitivity. Our findings indicate that the molecular structure of the BBB adapts to dietary changes, influencing glucose and insulin transport differently

(3) We demonstrate that a high-fat diet (HFD) quickly reduces Notch1 signaling in hypothalamic brain microvascular endothelial cells (BMECs), leading to impaired glucose uptake. Overexpressing the Notch intracellular domain in BMECs can maintain glucose uptake despite HFD exposure...

(2) By revealing the crucial role of endothelial Notch signaling in regulating glucose transporter expression, caveola formation, and BBB permeability, we identify a mechanism that explains how dietary signals influence brain insulin access and systemic insulin sensitivity.