Increased adiposity, dysregulated glucose metabolism and systemic inflammation in Galectin-3 KO mice

• Published in: PloS one 2013-02, Vol.8 (2), p.e57915-e57915
• Main Authors: Pang, Jingbo, Rhodes, Davina H, Pini, Maria, Akasheh, Rand T, Castellanos, Karla J, Cabay, Robert J, Cooper, Dianne, Perretti, Mauro, Fantuzzi, Giamila
• Format: Article
• Language: English
• Subjects: Acute phase proteins; Acute phase substances; Adducts; Adipocytes; Adiponectin; Adiponectin - genetics; Adiponectin - metabolism; Adipose tissue; Adiposity - genetics; Adiposity - physiology; Age; Anemia; Animals; Antibiotics; Biology; Blood glucose test; Cytokines; Diabetes; Diabetes mellitus; Diet; Fasting; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Galectin 3 - deficiency; Galectin 3 - genetics; Galectin 3 - metabolism; Galectin-3; Glucose; Glucose - genetics; Glucose - metabolism; Glucose tolerance; Glucose tolerance test; Glucose Tolerance Test - methods; Heart failure; Hyperglycemia; Inflammation; Inflammation - genetics; Inflammation - metabolism; Insulin; Insulin - genetics; Insulin - metabolism; Insulin Resistance - genetics; Kinesiology; Laboratory testing; Lipase - genetics; Lipase - metabolism; Liver; Liver - metabolism; Medical research; Medicine; Metabolism; Mice; Mice, Knockout; Mice, Obese; Microbiota; Microflora; Monocytes; Monocytes - metabolism; Neutrophilia; Nutrition research; Obesity; Obesity - genetics; Obesity - metabolism; Oxidative stress; Pathology; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Physiological aspects; PPAR gamma - genetics; PPAR gamma - metabolism; Proteins; Rodents; Statistics; Thrombocytosis; Transcription Factors - genetics; Transcription Factors - metabolism; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0057915

Obesity and type 2 diabetes are associated with increased production of Galectin-3 (Gal-3), a protein that modulates inflammation and clearance of glucose adducts. We used Lean and Diet-induced Obese (DIO) WT and Gal-3 KO mice to investigate the role of Gal-3 in modulation of adiposity, glucose metabolism and inflammation. Deficiency of Gal-3 lead to age-dependent development of excess adiposity and systemic inflammation, as indicated by elevated production of acute-phase proteins, number of circulating pro-inflammatory Ly6C(high) monocytes and development of neutrophilia, microcytic anemia and thrombocytosis in 20-week-old Lean and DIO male Gal-3 KO mice. This was associated with impaired fasting glucose, heightened response to a glucose tolerance test and reduced adipose tissue expression of adiponectin, Gal-12, ATGL and PPARγ, in the presence of maintained insulin sensitivity and hepatic expression of gluconeogenic enzymes in 20-week-old Gal-3 KO mice compared to their diet-matched WT controls. Expression of PGC-1α and FGF-21 in the liver of Lean Gal-3 KO mice was comparable to that observed in DIO animals. Impaired fasting glucose and altered responsiveness to a glucose load preceded development of excess adiposity and systemic inflammation, as demonstrated in 12-week-old Gal-3 KO mice. Finally, a role for the microflora in mediating the fasting hyperglycemia, but not the excessive response to a glucose load, of 12-week-old Gal-3 KO mice was demonstrated by administration of antibiotics. In conclusion, Gal-3 is an important modulator of glucose metabolism, adiposity and inflammation.