Ablation of <i>Prdm16</i> and beige fat identity causes vascular remodeling and elevated blood pressure
Mascha Koenen, Tobias Becher, Giulia Pagano, Ilaria Del Gaudio, Jorge A. Barrero, Augusto C. Montezano, Jenelys Ruiz Ortiz, Zeran Lin, Nicolás Gómez-Banoy, Rose Amblard, Daniel Schriever, Meltem Ece Kars, Luisa Rubinelli, Sarah J Halix, Zhen Fang Huang Cao, Xing Zeng, Scott D. Butler, Yuval Itan, Rhian M. Touyz, Annarita Di Lorenzo, Paul Cohen
Abstract
Excess adiposity is a major risk factor for hypertension and heart disease. Brown fat is associated with protection from cardiovascular pathology, but whether this relationship is causal remains unknown. In this work, we investigate the role of mouse beige fat, as a model of human inducible brown fat, in adipocyte-vascular cross-talk. Using adipocyte-specific Prdm16 knockout mice with a loss of beige adipocyte identity, we discovered marked remodeling of perivascular adipose tissue, increased vascular reactivity, and elevated blood pressure. We show that the circulating enzyme QSOX1 is derepressed in Prdm16 -deficient adipocytes, and deletion of Qsox1 in Prdm16 conditional knockout mice prevented vascular fibrosis and normalized vascular reactivity. These results demonstrate a key role for beige adipocytes in blood pressure regulation and identify QSOX1 as an important mediator of adipocyte-vascular cross-talk.