Increased Adiposity, Dysregulated Glucose Metabolism and Systemic Inflammation in Galectin-3 KO Mice

Pang, Jingbo; Rhodes, Davina H.; Pini, Maria; Akasheh, Rand T.; Castellanos, Karla J.; Cabay, Robert J.; Cooper, Dianne; Perretti, Mauro; Fantuzzi, Giamila
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
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 Ly6Chigh 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.


Related Articles

  • Protein Array Reveals Differentially Expressed Proteins in Subcutaneous Adipose Tissue in Obesity. �kopkov�, Martina; Penesov�, Adela; Sell, Henrike; R�dikov�, �ofia; Vlcek, Miroslav; Imrich, Richard; Ko�ka, Juraj; Ukropec, Jozef; Eckel, J�rgen; Klime�, Iwar; Ga�per�kov�, Daniela // Obesity (19307381);Oct2007, Vol. 15 Issue 10, p2396 

    The article deals with a study which aimed to provide new information about very early abnormalities in the adipose tissue proteomic profile and to link obesity to inflammation and early signs of insulin resistance in obese subjects. Participants in the study included young, clinically healthy,...

  • Dietary Advanced Glycation End Products Consumption as a Direct Modulator of Insulin Sensitivity in Overweight Humans: A Study Protocol for a Double-Blind, Randomized, Two Period Cross-Over Trial. de Courten, Barbora; de Courten, Maximilian P. J.; Schalkwijk, Casper G.; Walker, Karen Z.; Forbes, Josephine // Journal of Medical Internet Research;Jul2015, Vol. 17 Issue 7, p1 

    Background: Advanced glycation end products (AGEs) are formed during the processing, storage, and cooking of foods. As part of a western diet, AGEs are consumed in excess and impair glucose metabolism in patients with type 2 diabetes. In the absence of diabetes, AGE-mediated decreases in insulin...

  • The Proton-Activated Receptor GPR4 Modulates Glucose Homeostasis by Increasing Insulin Sensitivity. Giudici, Luca; Velic, ana; Daryadel, arezoo; Bettoni, Carla; Mohebbi, Nilufar; Suply, Thomas; Seuwen, Klaus; Ludwig, Marie-Gabrielle; Wagner, Carsten a. // Cellular Physiology & Biochemistry (Karger AG);Dec2013, Vol. 32 Issue 5, p1403 

    Background: The proton-activated G protein-coupled receptor GPR4 is expressed in many tissues including white adipose tissue. GPR4 is activated by extracellular protons in the physiological pH range (i.e. pH 7.7 - 6.8) and is coupled to the production of cAMP. Methods: We examined mice lacking...

  • Vaspin inhibits kallikrein 7 by serpin mechanism. Heiker, John; Klöting, Nora; Kovacs, Peter; Kuettner, E.; Sträter, Norbert; Schultz, Stephan; Kern, Matthias; Stumvoll, Michael; Blüher, Matthias; Beck-Sickinger, Annette // Cellular & Molecular Life Sciences;Jul2013, Vol. 70 Issue 14, p2569 

    The molecular target of the adipokine vaspin (visceral adipose tissue-derived serpin; serpinA12) and its mode of action are unknown. Here, we provide the vaspin crystal structure and identify human kallikrein 7 (hK7) as a first protease target of vaspin inhibited by classical serpin mechanism...

  • Decreased Insulin Clearance in Individuals with Elevated 1-h Post-Load Plasma Glucose Levels. Marini, Maria Adelaide; Frontoni, Simona; Succurro, Elena; Arturi, Franco; Fiorentino, Teresa Vanessa; Sciacqua, Angela; Hribal, Marta Letizia; Perticone, Francesco; Sesti, Giorgio // PLoS ONE;Oct2013, Vol. 8 Issue 10, p1 

    Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥8.6 mmol/l (155 mg/dl) at 1 h during an oral glucose tolerance test (OGTT) can identify individuals at high risk for type 2 diabetes...

  • Chronic Olanzapine Treatment Induces Disorders of Plasma Fatty Acid Profile in Balb/c Mice: A Potential Mechanism for Olanzapine-Induced Insulin Resistance. Li, Huqun; Fang, Maosheng; Xu, Mingzhen; Li, Shihong; Du, Juan; Li, Weiyong; Chen, Hui // PLoS ONE;12/14/2016, Vol. 11 Issue 12, p1 

    Background: Atypical antipsychotics such as olanzapine cause metabolic side effects leading to obesity and insulin resistance. The underlying mechanisms remain elusive. In this study we investigated the effects of chronic treatment of olanzapine on the fatty acid composition of plasma in mice....

  • Oral Treatment with γ-Aminobutyric Acid Improves Glucose Tolerance and Insulin Sensitivity by Inhibiting Inflammation in High Fat Diet-Fed Mice. Tian, Jide; Dang, Hoa N.; Jing Yong; Wing-Sheung Chui; Dizon, Matthew P. G.; Yaw, Catherine K. Y.; Kaufman, Daniel L. // PLoS ONE;2011, Vol. 6 Issue 9, p1 

    Adipocyte and b-cell dysfunction and macrophage-related chronic inflammation are critical for the development of obesityrelated insulin resistance and type 2 diabetes mellitus (T2DM), which can be negatively regulated by Tregs. Our previous studies and those of others have shown that activation...

  • Effect of Prolonged Intermittent Hypoxia and Exercise Training on Glucose Tolerance and Muscle GLUT4 Protein Expression in Rats. Li-Ling Chiu; Shih-Wei Chou; Yu-Min Cho; Hsin-Yi Ho; Ivy, John L.; Hunt, Desmond; Wang, Paulus S.; Chia-Hua Kuo // Journal of Biomedical Science;Nov/Dec2004, Vol. 11 Issue 6, p838 

    We compared the chronic effect of intermittent hypoxia and endurance training on the glucose tolerance and GLUT4 protein expression in rat skeletal muscle. Thirty-two Sprague-Dawley rats were matched for weight and assigned to one of the following four groups: control, endurance training,...

  • FFA2 Contribution to Gestational Glucose Tolerance Is Not Disrupted by Antibiotics. Fuller, Miles; Li, Xiaoran; Fisch, Robert; Bughara, Moneb; Wicksteed, Barton; Kovatcheva-Datchary, Petia; Layden, Brian T. // PLoS ONE;12/13/2016, Vol. 11 Issue 12, p1 

    During the insulin resistant phase of pregnancy, the mRNA expression of free fatty acid 2 receptor (Ffar2) is upregulated and as we recently reported, this receptor contributes to insulin secretion and pancreatic beta cell mass expansion in order to maintain normal glucose homeostasis during...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics