title: Galectin-12 enhances inflammation by promoting M1 polarization of macrophages and reduces insulin sensitivity in adipocytes.
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 pro-inflammatory 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.
authors.affiliation: School of Chinese Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan.|Department of Biotechnology, Asia University, Taichung, Taiwan.|Department of Gynecology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Lei
authors.initials: L
authors.lastname: Wan
authors.affiliation: School of Chinese Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan.|Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chi-Chun
authors.initials: CC
authors.lastname: Huang
authors.affiliation: School of Chinese Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan.|Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Ying-Chi
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine,National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Yu-An
authors.initials: YA
authors.lastname: Hsu
authors.affiliation: Institute of Molecular Medicine,National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan.|Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Hsiu-Chu
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Su-Hua
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Jane-Ming
authors.initials: JM
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Department of Dermatology, University of California, Davis, School of Medicine, 3301 C Street, Suite 1400, Sacramento, CA 95816, USA.
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000818:Animals; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016764:Cell Polarity / Q000235:genetics; D037161:Galectins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics*; D008262:Macrophage Activation / Q000235:genetics; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D050796:STAT3 Transcription Factor / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D037161:Galectins; D007328:Insulin; C503649:Lgals12 protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016753:Interleukin-10
keywords: Galectin-12; inflammation; macrophage polarization