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Chung, K.J.* ; Chatzigeorgiou, A.* ; Lim, J.H.* ; Li, X.* ; Marava, I.* ; Kim, D.Y.* ; Witt, A.* ; Gebler, J.* ; Grossklaus, S.* ; Gercken, B.* ; Kopaliani, I.* ; Subramanian, P.* ; Blüher, M. ; Bdeir, K.* ; Alexaki, V.I.* ; Hajishengallis, G.* ; Chavakis, T.

A DEL-1/αvβ3 integrin axis promotes brown adipocyte progenitor proliferation and cold-induced brown adipose tissue adaptation.

Mol. Metab. 100:102229 (2025)

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Cold-triggered adaptation of the brown adipose tissue (BAT) promotes increased non-shivering thermogenesis and helps maintain body temperature. Here, we demonstrate that the secreted protein developmental endothelial locus-1 (DEL-1) acts as a regulator of cold-induced BAT adaptation. DEL-1 was expressed in the vascular endothelium of the BAT and its expression was upregulated upon cold exposure. By interacting with αvβ3 integrin on brown adipocyte progenitor cells, DEL-1 promoted their proliferation in a manner dependent on AKT signaling and glycolysis activation. Compared to DEL-1-sufficient mice, DEL-1-deficient mice or mice expressing a non-integrin-binding mutant of DEL-1 carrying an Asp-to-Glu substitution in its RGD motif, displayed decreased cold tolerance. This phenotype was associated with impaired BAT adaptation to cold and reduced brown adipocyte progenitor cell proliferation. Conversely, endothelial-specific DEL-1 overexpression in DEL-1-deficient mice restored the BAT thermogenic response to cold. Together, the DEL-1/αvβ3 integrin-dependent endothelial-brown adipocyte progenitor cell crosstalk promotes cold-stimulated BAT adaptation. This knowledge could be potentially harnessed therapeutically for promoting BAT expansion towards improving systemic metabolism.

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Publication type Article: Journal article

Document type Scientific Article

Keywords Developmental Endothelial Locus-1 ; Brown Adipocyte Progenitor Proliferation ; Brown Adipose Tissue ; Cold-induced Brown Adipose Tissue Adaptation ; Integrins ; Thermogenesis; Developmental Endothelial Locus-1; Energy-expenditure; Glucose-uptake; Cell; Fat; Del-1; Bone; Differentiation; Thermogenesis; Recruitment

ISSN (print) / ISBN 2212-8778

e-ISSN 2212-8778

Journal Molecular Metabolism

Quellenangaben Volume: 100, Article Number: 102229

Publisher Elsevier

Publishing Place Amsterdam

Reviewing status Peer reviewed

Institute(s) Institute of Pancreatic Islet Research (IPI)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)

Grants NIH/NIDCR
German Center for Child and Adolescent Health
DZG Innovation Funds (Microbiome and Inter-Organ Metabolomics)
Tourism-SMWK (Sonderzuweisung zur Unterstuetzung profilbestimmender Struktureinheiten der TUD)
Saxon State Ministry of Science, Culture