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

MALLER, SEBASTIÁN M.; CAGNONI, ALEJANDRO; BANNOUD, NADIA; SIGAUT, LORENA; PÉREZ SÁEZ, JUAN MANUEL; PETRASANTA, LIA; YANG, R-Y.; LIU, F-T.; CROCI, DIEGO OMAR; DI LELLA, SANTIAGO; SUNDBLAD, VICTORIA; RABINOVICH, GABRIEL ADRIÁN; MARIÑO, KARINA

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

Lugar: Bethesda; Año: 2020 vol. 34 p. 735 - 753

0892-6638

Upon overnutrition, adipocytes activate ahomeostatic program to adjust anabolic pressure. An inflammatoryresponse enables adipose tissue (AT) expansion with concomitantenlargement of its capillary network, and reduces energy storage byincreasing insulin resistance. Galectin-12 (Gal-12), an endogenouslectin preferentially expressed in AT, plays a key role in adipocytedifferentiation, lipolysis and glucose homeostasis. Here, we revealbiochemical and biophysical determinants of Gal-12 structure,including its preferential recognition of 3-fucosylated structures, aunique feature among members of the galectin family. Furthermore, weidentify a previously unanticipated role for this lectin in theregulation of angiogenesis within AT. Gal-12 showed preferentiallocalization within the inner side of lipid droplets, and itsexpression was upregulated under hypoxic conditions. Throughglycosylation-dependent binding to endothelial cells, Gal-12 promotedin vitro angiogenesis.Moreover, analysis of in vivoAT vasculature showed reduced vascular networks in Gal-12-deficient(Lgals12-/-)compared to wild-type mice, supporting a role for this lectin in ATangiogenesis. In conclusion, this study unveils biochemical,topological and functional features of a hypoxia-regulated galectinin AT, which modulates endothelial cell function through recognitionof 3-fucosylated glycans. Thus, glycosylation-dependent programs maycontrol AT homeostasis by modulating endothelial cell biology withcritical implications in metabolic disorders and inflammation. p { margin-left: 0in; text-indent: 0in; margin-bottom: 0.1in; direction: ltr; color: rgb(0, 0, 0); line-height: 115%; }p.western { font-family: "Times New Roman", serif; font-size: 12pt; }p.cjk { font-family: "Times New Roman", serif; font-size: 12pt; }p.ctl { font-family: "Times New Roman", serif; font-size: 12pt; }