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

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Objectives Cold-triggered adaptation of the brown adipose tissue (BAT) promotes increased non-shivering thermogenesis and helps maintain body temperature. This study investigated the role of the secreted protein developmental endothelial locus-1 (DEL-1) in regulating BAT adaptation to cold. Methods DEL-1 expression in BAT was assessed following cold exposure in mice. The role of DEL-1 in cold-induced BAT adaptation, thermogenesis and proliferation of brown adipocyte progenitor cells was analyzed by utilizing genetically modified mouse models. Mechanistic insights into DEL-1-mediated regulation of brown adipocyte progenitor proliferation were obtained through in vitro assays. Results 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 B

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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