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Galectin-3 Deficiency Accelerates High-Fat Diet Induced Obesity and Amplifies Inflammation in Adipose Tissue and Pancreatic Islets.
MedLine Citation:
PMID:  23349493     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Obesity-induced diabetes is associated with low-grade inflammation in adipose tissue and macrophage infiltration of islets. We show that ablation of Galectin-3, a galactoside-binding lectin, accelerates high-fat diet-induced obesity and diabetes. Obese LGALS3(-/-) mice have increased body weight, amount of total visceral adipose tissue, fasting blood glucose and insulin levels, HOMA-IR and markers of systemic inflammation compared to diet-matched WT animals. Obese LGALS3(-/-) visceral adipose tissue exhibited increased incidence of Type-1 T and NKT lymphocytes and pro-inflammatory CD11c+CD11b macrophages and decreased CD4+CD25+FoxP3+ Tregs and M2 macrophages. Pronounced mononuclear cell infiltrate, increased expression of NLRP3 inflammasome and IL-1β in macrophages and increased accumulation of advanced glycation endproducts (AGE) and receptor for AGE (RAGE) expression were present in pancreatic islets of obese LGALS3(-/-) animals accompanied with elevated phosphorilated NFκB p65 and mature Caspase-1 protein expression in pancreatic and visceral adipose tissue. In vitro stimulation of LGALS3(-/-) peritoneal macrophages with lypopolysaccharide (LPS) and saturated fatty acid palmitate caused increased Caspase-1 dependent IL-1β production and increased phosphorilation of NFκB p65 compared to WT cells. Transfection of LGALS3(-/-) macrophages with NLRP3 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.
Authors:
Nada Pejnovic; Jelena Pantic; Ivan Jovanovic; Gordana Radosavljevic; Marija Milovanovic; Ivana Nikolic; Nemanja Zdravkovic; Aleksandar Djukic; Nebojsa Arsenijevic; Miodrag Lukic
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  Diabetes     Volume:  -     ISSN:  1939-327X     ISO Abbreviation:  Diabetes     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Faculty of Medicine, Center for Molecular Medicine and Stem Cell Research, Kragujevac, Serbia.
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