Galectin-12 enhances inflammation by promoting M1 polarization of macrophages and reduces insulin sensitivity in adipocytes

Lei Wan, Hui Ju Lin, Chi Chun Huang, Ying Chi Chen, Yu An Hsu, Chia Hung Lin, Hsiu Chu Lin, Ching Yao Chang, Su Hua Huang, Jane Ming Lin, Fu-Tong Liu

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Galectin-12 is a member of an animal lectin family with affinity for β-galactosides and containing consensus amino acid sequences. Here, we found that galectin-12 was expressed in macrophages and thus aimed to determine how galectin-12 affects inflammation and macrophage polarization and activation. The ablation of galectin-12 did not affect bone marrow cells to differentiate into macrophages, but reduced phagocytic activity against Escherichia coli and lowered the secretion of nitric oxide. The ablation of galectin-12 also resulted in the polarization of macrophages into the M2 direction, as indicated by increases in the levels of M2 markers, namely, resistin-like β (FIZZ1) and chitinase 3-like 3 (Ym1), as well as a reduction in the expression levels of a number of M1 proinflammatory cytokines. We found that the diminished expression of pro-inflammatory cytokines in macrophages resulting from galectin-12 deletion was due to reduced activation of IKKα/β, Akt and ERK, which in turn caused decreased activation of NF-κB and activator protein 1. The activation of STAT3 was much higher in Gal12-/- macrophages activated by lipopolysaccharide, which was correlated with higher levels of IL-10. Adipocytes showed higher insulin sensitivity when treated with Gal12-/- macrophage-conditioned media than those treated with Gal12+/+ macrophages. We conclude galectin-12 negatively regulates macrophage polarization into the M2 population, resulting in enhanced inflammatory responses and also in turn causing decreased insulin sensitivity in adipocytes. This has implications in the treatment of a wide spectrum of metabolic disorders.

Original languageEnglish (US)
Pages (from-to)732-744
Number of pages13
JournalGlycobiology
Volume26
Issue number7
DOIs
StatePublished - Jul 1 2016

Keywords

  • Galectin-12
  • Inflammation
  • Macrophage polarization

ASJC Scopus subject areas

  • Biochemistry

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    Wan, L., Lin, H. J., Huang, C. C., Chen, Y. C., Hsu, Y. A., Lin, C. H., Lin, H. C., Chang, C. Y., Huang, S. H., Lin, J. M., & Liu, F-T. (2016). Galectin-12 enhances inflammation by promoting M1 polarization of macrophages and reduces insulin sensitivity in adipocytes. Glycobiology, 26(7), 732-744. https://doi.org/10.1093/glycob/cww013