Ablation of <i>Prdm16</i> 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 <i>Prdm16</i> 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 <i>Prdm16</i>-deficient adipocytes, and deletion of <i>Qsox1</i> in <i>Prdm16</i> 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.
Authors
- Augusto C. Montezano (ORCID: https://orcid.org/0000-0002-8658-7994)
- Ilaria Del Gaudio (ORCID: https://orcid.org/0000-0001-6794-8291)
- Rhian M. Touyz (ORCID: https://orcid.org/0000-0003-0670-0887)
- Zeran Lin (ORCID: https://orcid.org/0000-0003-4418-2443)
- Xing Zeng
- Meltem Ece Kars (ORCID: https://orcid.org/0000-0001-5922-5608)
- Scott D. Butler
- Nicolás Gómez-Banoy (ORCID: https://orcid.org/0000-0002-3552-1768)
- Mascha Koenen (ORCID: https://orcid.org/0000-0002-1024-4506)
- Luisa Rubinelli
- Giulia Pagano (ORCID: https://orcid.org/0000-0003-2395-4731)
- Tobias Becher (ORCID: https://orcid.org/0000-0001-7670-757X)
- Jorge A. Barrero (ORCID: https://orcid.org/0000-0003-2958-5551)
- Jenelys Ruiz Ortiz
- Zhen Fang Huang Cao
- Rose Amblard
- Sarah J Halix
- Annarita Di Lorenzo
- Daniel Schriever
- Paul Cohen
Institutions
- Mount Sinai Health System (US)
- Memorial Sloan Kettering Cancer Center (US)
- Cornell University (US)
- Heidelberg University (DE)
- McGill University Health Centre (CA)
- University Hospital Heidelberg (DE)
- Universidad Nacional de Colombia (CO)
- Southwestern Medical Center (US)
- MIND Research Institute (US)
- Child Health and Development Institute (US)
- University Medical Centre Mannheim (DE)
- Weill Cornell Medicine (US)
- Heinrich Heine University Düsseldorf (DE)
- Rockefeller University (US)
- The University of Texas Southwestern Medical Center (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Science
- Published
- 2026-01-15
- DOI
- https://doi.org/10.1126/science.ady8644
- Citations
- 3
- Primary Topic
- Cardiovascular Disease and Adiposity
- Type
- article
- Field-Weighted Citation Impact
- 90.20