Galectin-3 deficiency accelerates high-fat diet induced obesity and diabetes by amplifying metaflammation
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1
Faculty of Medical Sciences University of Kragujevac , Serbia
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2
Institute for Biological Research ‘Sinisa Stankovic’, University of Belgrade, Serbia
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3
Center for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center Kragujevac, Serbia
Obesity-induced diabetes is associated with low-grade inflammation in adipose tissue and infiltration of macrophages in pancreatic islets. Galectin-3 (Gal-3), a galactoside-binding lectin, has a role in inflammation, uptake and removal of metabolic compounds. We show that ablation of Gal-3 accelerates high-fat diet-induced obesity and diabetes. Wild-type and LGALS3-/- mice on a C57BL/6J background were fed either high-fat (60% fat) or a low-fat diet (3% fat) for 11 or 18 weeks. The increased body weight, amount of total visceral adipose tissue (VAT), fasting blood glucose and insulin levels, homeostasis model assessment of insulin resistance and systemic inflammation were observed in high-fat diet-fed LGALS3-/- mice compared to diet-matched WT animals. Obese LGALS3-/- mice had increased incidence of Type-1 T and NKT lymphocytes and pro-inflammatory CD11c+CD11b+ macrophages and decreased CD4+CD25+FoxP3+ Tregs and M2 macrophages in VAT. The severe insulitis, increased expression of NLRP3 inflammasome and IL-1ß in macrophages and increased accumulation of advanced glycation endproducts (AGE) and receptor for AGE (RAGE) expression in pancreatic islets of obese LGALS3-/- animals were associated with elevated expression of phospho-NFκB p65 and mature Caspase-1 protein in pancreata and VAT. LGALS3-/- peritoneal macrophages stimulated with lypopolysaccharide (LPS) and saturated fatty acid palmitate in vitro produced increased Caspase-1 dependent IL-1β and had increased expression of NLRP3 inflammasome and phospho-NFκB p65 compared to WT macrophages. Transfection of LGALS3-/- macrophages with NLRP3 inflammasome siRNA attenuated IL-1β production in response to palmitate and LPS plus palmitate. Obtained results suggest important protective roles for Gal-3 in obesity-induced inflammation and diabetes.
This work was supported by grants from the Serbian Ministry of Science and Technological Development (175071 and 175069), Belgrade, Serbia.
Keywords:
galectin-3,
Obesity,
type 2 diabetes,
Inflammation,
Insulin Resistance,
NLRP3 inflammasome,
NF-κB,
IL-1β
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Pejnovic
N,
Pantic
J,
Jovanovic
I,
Radosavljevic
G,
Milovanovic
M,
Nikolic
I,
Zdravkovic
N,
Djukic
A,
Arsenijevic
N and
Lukic
ML
(2013). Galectin-3 deficiency accelerates high-fat diet induced obesity and diabetes by amplifying metaflammation.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00681
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Received:
12 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Prof. Miodrag L Lukic, Faculty of Medical Sciences University of Kragujevac, Kragujevac, Serbia, miodrag.lukic@medf.kg.ac.rs