TY - JOUR
T1 - An adipose tissue galectin controls endothelial cell function via preferential recognition of 3-fucosylated glycans
AU - Maller, Sebastián M.
AU - Cagnoni, Alejandro J.
AU - Bannoud, Nadia
AU - Sigaut, Lorena
AU - Pérez Sáez, Juan M.
AU - Pietrasanta, Lía I.
AU - Yang, Ri Yao
AU - Liu, Fu Tong
AU - Croci, Diego O.
AU - Di Lella, Santiago
AU - Sundblad, Victoria
AU - Rabinovich, Gabriel A.
AU - Mariño, Karina V.
N1 - Publisher Copyright:
© 2019 Federation of American Societies for Experimental Biology
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - adipose tissue
KW - angiogenesis
KW - galectins
KW - glycosylation
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U2 - 10.1096/fj.201901817R
DO - 10.1096/fj.201901817R
M3 - Article
C2 - 31914594
AN - SCOPUS:85077737453
SN - 0892-6638
VL - 34
SP - 735
EP - 753
JO - FASEB Journal
JF - FASEB Journal
IS - 1
ER -