An adipose tissue galectin controls endothelial cell function via preferential recognition of 3‐fucosylated glycans

MALLER, SEBASTIÁN M.; SIGAUT, LORENA; YANG, RI-YAO; DI LELLA, SANTIAGO; MARIÑO, KARINA V.; CAGNONI, ALEJANDRO J.; PÉREZ SÁEZ, JUAN M.; LIU, FU-TONG; SUNDBLAD, VICTORIA; BANNOUD, NADIA; PIETRASANTA, LÍA I.; CROCI, DIEGO O.; RABINOVICH, GABRIEL A.

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

Lugar: Bethesda; Año: 2019 vol. 34 p. 735 - 753

0892-6638

Abstract Upon overnutrition, adipocytes activate a homeostatic program to adjust anabolic pressure. An inflammatory response enables adipose tissue expansion with the concomitant enlargement of its capillary network, and reduces energy storage by increasing insulin resistance. Galectin-12 (Gal-12), an endogenous lectin preferentially expressed in adipose tissue, 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 adipose tissue. 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 adipose tissue vasculature showed reduced vascular networks in Gal-12-deficient (Lgals12-/-) compared to wild-type mice, supporting the role of this lectin in adipose tissue angiogenesis. In conclusion, this study unveils biochemical, topological and functional features of a hypoxia-regulated galectin in adipose tissue, which modulates endothelial cell function through preferential recognition of 3-fucosylated glycans. Thus, glycosylation-dependent programs may control adipose tissue homeostasis by modulating endothelial cell biology.