Ablation of Prdm16 and beige fat identity causes vascular remodeling and elevated blood pressure.

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. Editor's summary: Although adiposity is generally correlated with the risk of hypertension, not all adipose tissue is equivalent, and there are two types of metabolically healthier adipose tissue: brown and beige. Of these, beige fat is the more relevant one for adult humans. The protein PRDM16 is known to regulate beige adipocyte biogenesis. Koenen et al. identified a role for PRDM16 in blood pressure regulation (see the Perspective by Grootaert and Luttun). Using mouse models and genetic data from patients, the authors showed that the activity of PRDM16 and the presence of beige fat were necessary for maintaining healthy blood pressure through the secretion of a protein called QSOX1, which is involved in vascular remodeling. Conversely, the loss of PRDM16 caused both depletion of beige adipocytes and dysregulation of blood pressure. —Yevgeniya Nusinovich [ABSTRACT FROM AUTHOR]