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

• 成果类型: Article
• 署名作者: Koenen, Mascha; Becher, Tobias; Pagano, Giulia; Del Gaudio, Ilaria; Barrero, Jorge A.; Montezano, Augusto C.; Ortiz, Jenelys Ruiz; Lin, Zeran; Gomez-Banoy, Nicolas; Amblard, Rose; Schriever, Daniel; Kars, Meltem E.; Rubinelli, Luisa; Halix, Sarah J.; Cao, Zhen Fang Huang; Zeng, Xing; Butler, Scott D.; Itan, Yuval; Touyz, Rhian M.; Di Lorenzo, Annarita; Cohen, Paul
• 署名单位: Rockefeller University; Ruprecht Karls University Heidelberg; Cornell University; Weill Cornell Medicine; Universidad Nacional de Colombia; McGill University; Rockefeller University; Cornell University; Weill Cornell Medicine; Memorial Sloan Kettering Cancer Center; Heinrich Heine University Dusseldorf; Icahn School of Medicine at Mount Sinai; University of Texas System; University of Texas Southwestern Medical Center; Cornell University; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.ady8644
• 发表日期: 2026-01-15
• 页码: 306-313
• 关键词: brown adipose-tissue; SMOOTH-MUSCLE-CELLS; functional-characterization; hypertension; resistance; individuals; phenotype; stiffness; fibrosis; linking

摘要

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.