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

Koenen, M.; Becher, T.; Pagano, G.; Del Gaudio, I.; Barrero, J. A.; Montezano, A. C.; Ortiz, J. R.; Lin, Z.; Gomez-Banoy, N.; Amblard, R.; Kars, M. E.; Rubinelli, L.; Halix, S. J.; Cao, Z. H.; Zeng, X.; Butler, S. D.; Itan, Y.; Touyz, R. M.; Di Lorenzo, A.; Cohen, P.

doi:10.1101/2025.06.12.658904

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bioRxiv · 10.1101/2025.06.12.658904

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

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Abstract

While excess adiposity is a major risk factor for hypertension and cardiovascular disease, brown fat is associated with protection from these pathologies. Whether brown fat has a causal role in this process and the underlying molecular mechanisms remain unknown. Here we investigate the role of murine beige fat, as a model of inducible brown fat in humans, in adipocyte-vascular crosstalk. Using mice with an adipocyte-specific deletion of PRDM16, resulting in a loss of beige adipocyte identity, we discover a dramatic remodeling of perivascular adipose tissue, increased vascular reactivity and elevated blood pressure. We further show that the circulating enzyme Qsox1 is de-repressed in Prdm16-deficient adipocytes, and deletion of Qsox1 in PRDM16cKO mice rescues vascular fibrosis and reactivity. These results demonstrate a key new role for beige adipocytes in blood pressure regulation and identify Qsox1 as an important mediator of adipocyte-vascular crosstalk.

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Koenen, M., Becher, T., Pagano, G., Del Gaudio, I., Barrero, J. A., Montezano, A. C., Ortiz, J. R., Lin, Z., Gomez-Banoy, N., Amblard, R., Kars, M. E., Rubinelli, L., Halix, S. J., Cao, Z. H., Zeng, X., Butler, S. D., Itan, Y., Touyz, R. M., Di Lorenzo, A., Cohen, P.. 2025-06-17. Ablation of Prdm16 and beige fat causes vascular remodeling and elevated blood pressure. https://doi.org/10.1101/2025.06.12.658904

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