Abstract
Previously, galectin-1 (GAL1) was found to be up-regulated in obesity-prone subjects, suggesting that use of a GAL1 inhibitor could be a novel therapeutic approach for treatment of obesity. We evaluated thiodigalactoside (TDG) as a potent inhibitor of GAL1 and identified target proteins of TDG by performing comparative proteome analysis of white adipose tissue (WAT) from control and TDG-treated rats fed a high fat diet (HFD) using two dimensional gel electrophoresis (2-DE) combined with MALDI-TOF-MS. Thirty-two spots from a total of 356 matched spots showed differential expression between control and TDG-treated rats, as identified by peptide mass fingerprinting. These proteins were categorized into groups such as carbohydrate metabolism, tricarboxylic acid (TCA) cycle, signal transduction, cytoskeletal, and mitochondrial proteins based on functional analysis using Protein Annotation Through Evolutionary Relationship (PANTHER) and Database for Annotation, Visualization, Integrated Discovery (DAVID) classification. One of the most striking findings of this study was significant changes in Carbonic anhydrase 3 (CA3), Voltage-dependent anion channel 1 (VDAC1), phosphatidylethanolamine-binding protein 1 (PEBP1), annexin A2 (ANXA2) and lactate dehydrogenase A chain (LDHA) protein levels between WAT from control and TDG-treated groups. In addition, we confirmed increased expression of thermogenic proteins as well as reduced expression of lipogenic proteins in response to TDG treatment. These results suggest that TDG may effectively prevent obesity, and TDG-responsive proteins can be used as novel target proteins for obesity treatment.
Highlights
Obesity results from continuous imbalance between energy intake and energy expenditure
We evaluated the anti-obesity effects of TDG in high fat diet (HFD) induced obese rats by treatment with 5 mg/kg of TDG for five weeks
There are other known targets of thiodigalactoside, such as heat-labile enterotoxin b chain, neurocan core protein and lactose permease, but this study only focused on GAL1 as a target of TDG
Summary
Obesity results from continuous imbalance between energy intake and energy expenditure. White adipose tissue (WAT) plays an important role in the progression of obesity and metabolic diseases. Taken together, targeted inhibition of GAL1 may help prevent obesity Glycoconjugates such as galactose, lactose, and thiodigalactoside (TDG) as well as some peptides such as davant and anginex are known to display different binding affinities for galectin family members and act as binding inhibitors [15,16]. Two-dimensional electrophoresis (2-DE) coupled with MALDI-TOF-MS is considered to be a powerful tool for the separation of adipose tissue proteins [20,21,22] This approach could possibly be used to identify novel biomarkers related to obesity treatment. To the best of our knowledge, this is the first proteomic study of WAT upon TDG treatment in an obese animal model
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