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Serdan, T.D.A.* ; Cervantes, H.* ; Frank, B.* ; Iragavarapu, A.G.* ; Tian, Q.* ; Hope, D.* ; Choi, C.H.J.* ; Hoffmann, A. ; Ghosh, A.* ; Wolfrum, C.* ; Greenblatt, M.B.* ; Cohen, P.* ; Blüher, M. ; Aydin, H.* ; Schwartz, G.J.* ; Shamsi, F.*

SLIT3 fragments orchestrate neurovascular expansion and thermogenesis in brown adipose tissue.

Nat. Commun. 17:2445 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Brown adipose tissue is an evolutionary innovation in placental mammals that regulates body temperature through adaptive thermogenesis. Cold exposure activates brown adipose tissue thermogenesis through coordinated induction of brown adipogenesis, angiogenesis, and sympathetic innervation; however, how these processes are coordinated remains unclear. Here, we show that fragments of Slit guidance ligand 3 (SLIT3) drive crosstalk among adipocyte progenitors, endothelial cells, and sympathetic nerves. Adipocyte progenitors secrete SLIT3, which is cleaved into functionally distinct SLIT3-N and SLIT3-C fragments that independently promote angiogenesis and sympathetic innervation. We identify PLXNA1 as a receptor for SLIT3-C and demonstrate its essential role in sympathetic innervation of brown adipose tissue. Moreover, we identify BMP1 as the first SLIT protease described in vertebrates. Coordinated neurovascular expansion mediated by distinct SLIT3 fragments provides a bifurcated yet integrated mechanism that ensures a synchronized brown adipose tissue response to environmental challenges. Finally, this study reveals a previously unrecognized role for adipocyte progenitors in regulating tissue innervation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Bone Morphogenetic Protein-1; Expression Patterns; Sympathetic-nerves; Rna-seq; Progenitors; Repellent; Guidance; Midline; Roles
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 17, Heft: 1, Seiten: , Artikelnummer: 2445 Supplement: ,
Verlag Springer
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Förderungen American Heart Association (American Heart Association, Inc.)
G. Harold and Leila Y. Mathers Foundation (G. Harold & Leila Y. Mathers Foundation)
U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)