Journal
FASEB JOURNAL
Volume 34, Issue 1, Pages 735-753Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201901817R
Keywords
adipose tissue; angiogenesis; galectins; glycosylation
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Funding
- CONICET
- Sales Foundation
- Bunge & Born Foundation
- Rene Baron Foundation
- Richard Lounsbery Foundation (USA)
- Agencia Nacional de Promocion Cientifica y Tecnologica [PICT 2015-0564, PICT V 2014-3687, PICT 2016-0205]
- University of Buenos Aires [20020120100276]
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Upon overnutrition, adipocytes activate a homeostatic program to adjust anabolic pressure. An inflammatory response enables adipose tissue (AT) expansion with concomitant enlargement of its capillary network, and reduces energy storage by increasing insulin resistance. Galectin-12 (Gal-12), an endogenous lectin preferentially expressed in AT, plays a key role in adipocyte differentiation, lipolysis, and glucose homeostasis. Here, we reveal biochemical and biophysical determinants of Gal-12 structure, including its preferential recognition of 3-fucosylated structures, a unique feature among members of the galectin family. Furthermore, we identify a previously unanticipated role for this lectin in the regulation of angiogenesis within AT. Gal-12 showed preferential localization within the inner side of lipid droplets, and its expression was upregulated under hypoxic conditions. Through glycosylation-dependent binding to endothelial cells, Gal-12 promoted in vitro angiogenesis. Moreover, analysis of in vivo AT vasculature showed reduced vascular networks in Gal-12-deficient (Lgals12(-/-)) compared to wild-type mice, supporting a role for this lectin in AT angiogenesis. In conclusion, this study unveils biochemical, topological, and functional features of a hypoxia-regulated galectin in AT, which modulates endothelial cell function through recognition of 3-fucosylated glycans. Thus, glycosylation-dependent programs may control AT homeostasis by modulating endothelial cell biology with critical implications in metabolic disorders and inflammation.
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