<abstract xmlns="http://www.w3.org/1999/xhtml">Obesity and type 2 diabetes mellitus (T2DM) constitute major health problems worldwide. Increased visceral adiposity enhances the risk of insulin resistance and type 2 diabetes. The mechanisms involved in obesity-associated chronic inflammation in metabolic tissues (metaflammation) that lead to insulin resistance and dysregulated glucose metabolism are incompletely defined. Galectin-3 (Gal-3), a β-galactoside-binding lectin, modulates immune/inflammatory responses and specifically binds to metabolic danger molecules. To dissect the role of Gal-3 in obesity and diabetes, Gal-3-deficient (LGALS3-/-) and wild-type (WT) C57Bl/6 male mice were placed on a high-fat diet (HFD, 60% kcal fat) or a standard chow diet (10% kcal fat) for 6 months and metabolic, histological and immunophenotypical analyses of the visceral adipose tissue were performed. HFD-fed LGALS3-/- mice had higher body weights and more body weight gain, visceral adipose tissue (VAT), hyperglycaemia, hyperinsulinemia, insulin resistance and hyperlipidemia than diet-matched WT mice. Compared to WT mice, the enlarged VAT in obese LGALS3-/- mice contained larger adipocytes. Additionally, we demonstrate enhanced inflammation in the VAT of LGALS3-/- mice compared with diet-matched WT mice. The VAT of LGALS3-/- mice fed a HFD contained more numerous dendritic cells and proinflammatory F4/80+CD11c+CD11b+ and F4/80high macrophages. In contrast to WT mice, the numbers of CXCR3+ and CD8+ T cells were increased in the VAT of Gal-3-deficient mice after 6 months of high-fat feeding. We provide evidence that Gal-3 ablation results in enhanced HFD-induced adiposity, inflammation in the adipose tissue, insulin resistance and hyperglycaemia. Thus, Gal-3 represents an important regulator of obesity-associated immunometabolic alterations.</abstract>

Obesity and type 2 diabetes mellitus (T2DM) constitute major health problems worldwide. Increased visceral adiposity enhances the risk of insulin resistance and type 2 diabetes. The mechanisms involved in obesity-associated chronic inflammation in metabolic tissues (metaflammation) that lead to insulin resistance and dysregulated glucose metabolism are incompletely defined. Galectin-3 (Gal-3), a β-galactoside-binding lectin, modulates immune/inflammatory responses and specifically binds to metabolic danger molecules. To dissect the role of Gal-3 in obesity and diabetes, Gal-3-deficient (LGALS3-/-) and wild-type (WT) C57Bl/6 male mice were placed on a high-fat diet (HFD, 60% kcal fat) or a standard chow diet (10% kcal fat) for 6 months and metabolic, histological and immunophenotypical analyses of the visceral adipose tissue were performed. HFD-fed LGALS3-/- mice had higher body weights and more body weight gain, visceral adipose tissue (VAT), hyperglycaemia, hyperinsulinemia, insulin resistance and hyperlipidemia than diet-matched WT mice. Compared to WT mice, the enlarged VAT in obese LGALS3-/- mice contained larger adipocytes. Additionally, we demonstrate enhanced inflammation in the VAT of LGALS3-/- mice compared with diet-matched WT mice. The VAT of LGALS3-/- mice fed a HFD contained more numerous dendritic cells and proinflammatory F4/80+CD11c+CD11b+ and F4/80high macrophages. In contrast to WT mice, the numbers of CXCR3+ and CD8+ T cells were increased in the VAT of Gal-3-deficient mice after 6 months of high-fat feeding. We provide evidence that Gal-3 ablation results in enhanced HFD-induced adiposity, inflammation in the adipose tissue, insulin resistance and hyperglycaemia. Thus, Gal-3 represents an important regulator of obesity-associated immunometabolic alterations.

Galectin-3 Deletion Enhances Visceral Adipose Tissue Inflammation and Dysregulates Glucose Metabolism in Mice on a High-Fat Diet

Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac,

Institute of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac,

Institute of Histology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac,

Experimental and Applied Biomedical Research (EABR)

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Obesity and type 2 diabetes mellitus (T2DM) constitute major health problems worldwide. Increased visceral adiposity enhances the risk of insulin resistance...

Galectin-3 Deletion Enhances Visceral Adipose Tissue Inflammation and Dysregulates Glucose Metabolism in Mice on a High-Fat Diet

Online veröffentlicht: 24. Sept. 2016

Seitenbereich: 231 - 240

Eingereicht: 16. Feb. 2016

Akzeptiert: 15. März 2016

DOI: https://doi.org/10.1515/sjecr-2016-0030

Schlüsselwörter
Galectin-3, obesity, hyperglycaemia, insulin resistance, metaflammation

© 2016 Ilija Jeftic et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Galectin-3 Deletion Enhances Visceral Adipose Tissue Inflammation and Dysregulates Glucose Metabolism in Mice on a High-Fat Diet

Online veröffentlicht: 24. Sept. 2016

Seitenbereich: 231 - 240

Eingereicht: 16. Feb. 2016

Akzeptiert: 15. März 2016

DOI: https://doi.org/10.1515/sjecr-2016-0030

SchlüsselwörterGalectin-3, obesity, hyperglycaemia, insulin resistance, metaflammation

© 2016 Ilija Jeftic et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Schlüsselwörter
Galectin-3, obesity, hyperglycaemia, insulin resistance, metaflammation