@misc{10481/109740,
year = {2021},
month = {6},
url = {https://hdl.handle.net/10481/109740},
abstract = {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 1α-vascular endothelial growth factor (HIF1α-VEGF) signaling downstream of leptin signaling. Importantly, several distinct models of HIF1α-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 HIF1α-VEGF signaling cascade in hypothalamic astrocytes while establishing a novel mechanistic link that connects hypothalamic micro-angioarchitecture with control over systemic blood pressure.},
organization = {Marie Skłodowska-Curie (ChroMe # 675610)},
organization = {European Research Council (Hypoflam # 695054, AstroNeuroCrosstalk #757393)},
organization = {German Research Foundation (EXC 2145 SyNergy – ID 390857198, SFB TRR152/P23, SFB TRR296)},
organization = {US National Institutes of Health (HL084207)},
organization = {University of Iowa (merit grant BX004249)},
organization = {Iowa Neuroscience Institute},
organization = {German Excellence Initiative/European Union Seventh Framework Programme 291763},
publisher = {Elsevier},
title = {Obesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension},
doi = {10.1016/j.cmet.2021.04.007},
author = {Gruber, Tim and Pan, Chenchen and Contreras, Raian Eduardo and Wiedemann, Tobias and Morgan, Donald A. and Skowronski, Alicja A. and lefort, Sandrine and Murat, Cahué De Bernadis and Le Thuc, Ophelia and Legutko, Beata and Ruiz Ojeda, Francisco Javier and Fuente-Fernández, María de la and García-Villalón, Ángel Luis and González-Hedstöm, Daniel and Huber, Melanie and Szigeti-Buck, Klara and Müller, Timo D. and Ussar, Siegfried and Pfluger, Paul and Woods, Steve C. and Ertück, Ali and LeDuc, Charles A. and Rahmouni, Kamal and Granado, Miriam and Horvarth, Tamas L. and Tschöp, Matthias H.},
}