Glycobiological axis in adipose tissue: structural, biochemical and functional characterization of Galectin-12

CAGNONI, ALEJANDRO J.

San Luis

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; 2019

Sociedad Argentina de Biofísica

Upon overnutrition, adipocytes activate a homeostatic program to adjust anabolicpressure. An inflammatory response enables adipose tissue (AT) expansion withconcomitant enlargement of its capillary network, and reduces energy storage byincreasing insulin resistance. Galectin-12 (Gal-12), an endogenous lectin preferentiallyexpressed in AT, plays a key role in adipocyte differentiation, lipolysis, andglucose homeostasis. Here, we reveal biochemical and biophysical determinants ofGal-12 structure, including its preferential recognition of 3-fucosylated structures,a unique feature among members of the galectin family. Furthermore, we identify apreviously unanticipated role for this lectin in the regulation of angiogenesis withinAT. 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 inGal-12-deficient (Lgals12-/-) compared to wild-type mice, supporting a role for thislectin in AT angiogenesis. In conclusion, this study unveils biochemical, topological,and functional features of a hypoxia-regulated galectin in AT, which modulatesendothelial cell function through recognition of 3-fucosylated glycans. Thus, glycosylation-dependent programs may control AT homeostasis by modulating endothelialcell biology with critical implications in metabolic disorders and inflammation.