| First Author | Gruber T | Year | 2021 |
| Journal | Cell Metab | Volume | 33 |
| Issue | 6 | Pages | 1155-1170.e10 |
| PubMed ID | 33951475 | Mgi Jnum | J:307393 |
| Mgi Id | MGI:6720693 | Doi | 10.1016/j.cmet.2021.04.007 |
| Citation | Gruber T, et al. (2021) Obesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension. Cell Metab 33(6):1155-1170.e10 |
| abstractText | Pathologies of the micro- and macrovascular systems are a hallmark of the metabolic syndrome, which can lead to chronically elevated blood pressure. However, the underlying pathomechanisms involved still need to be clarified. Here, we report that an obesity-associated increase in serum leptin triggers the select expansion of the micro-angioarchitecture in pre-autonomic brain centers that regulate hemodynamic homeostasis. By using a series of cell- and region-specific loss- and gain-of-function models, we show that this pathophysiological process depends on hypothalamic astroglial hypoxia-inducible factor 1alpha-vascular endothelial growth factor (HIF1alpha-VEGF) signaling downstream of leptin signaling. Importantly, several distinct models of HIF1alpha-VEGF pathway disruption in astrocytes are protected not only from obesity-induced hypothalamic angiopathy but also from sympathetic hyperactivity or arterial hypertension. These results suggest that hyperleptinemia promotes obesity-induced hypertension via a HIF1alpha-VEGF signaling cascade in hypothalamic astrocytes while establishing a novel mechanistic link that connects hypothalamic micro-angioarchitecture with control over systemic blood pressure. |
