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

Sebastián M. Maller, Alejandro J. Cagnoni, Nadia Bannoud, Lorena Sigaut, Juan M. Pérez Sáez, Lía I. Pietrasanta, Ri Yao Yang, Fu Tong Liu, Diego O. Croci, Santiago Di Lella, Victoria Sundblad, Gabriel A. Rabinovich, Karina V. Mariño

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)735-753
Number of pages19
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2020

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Keywords

  • adipose tissue
  • angiogenesis
  • galectins
  • glycosylation

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Maller, S. M., Cagnoni, A. J., Bannoud, N., Sigaut, L., Pérez Sáez, J. M., Pietrasanta, L. I., Yang, R. Y., Liu, F. T., Croci, D. O., Di Lella, S., Sundblad, V., Rabinovich, G. A., & Mariño, K. V. (2020). An adipose tissue galectin controls endothelial cell function via preferential recognition of 3-fucosylated glycans. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34(1), 735-753. https://doi.org/10.1096/fj.201901817R