title: Increased adiposity, dysregulated glucose metabolism and systemic inflammation in Galectin-3 KO mice.
abstract: 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.
authors: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Jingbo
authors: J
authors: Pang
authors: Davina H
authors: DH
authors: Rhodes
authors: Maria
authors: M
authors: Pini
authors: Rand T
authors: RT
authors: Akasheh
authors: Karla J
authors: KJ
authors: Castellanos
authors: Robert J
authors: RJ
authors: Cabay
authors: Dianne
authors: D
authors: Cooper
authors: Mauro
authors: M
authors: Perretti
authors: Giamila
authors: G
authors: Fantuzzi
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D050154:Adiposity / Q000235:genetics / Q000502:physiology*; D000818:Animals; D004032:Diet; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D037502:Galectin 3 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D005951:Glucose Tolerance Test / Q000379:methods; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D009000:Monocytes / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000217:Acyltransferases
chemical_list: D052242:Adiponectin; D005346:Fibroblast Growth Factors; D037502:Galectin 3; D005947:Glucose; D007328:Insulin; D008049:Lipase; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; C485290:Ppargc1a protein, mouse; C414620:fibroblast growth factor 21; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases