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Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Talabostat Alleviates Obesity and Associated Metabolic Dysfunction via Suppression of Macrophage-Driven Adipose
Yunyun Wu1, Tiancong Shi1, Jiqiu Wang2
1Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Objective:
Adipose tissue macrophages (ATMs) play critical roles in obesity-associated inflammation that contributes to metabolic dysfunction. Talabostat (TB) exerts some therapeutic effects on tumors and obesity. However, it remains unknown whether the metabolic benefits of TB on obesity is dependent on ATM-mediated adipose inflammation.
Methods:
Male C57BL/6J mice were fed a normal chow diet (NCD) or a high-fat diet for 12 weeks, and mice were orally administered TB daily at a low dose (0.5 mg/kg).
Results:
Administration of TB to mice fed a high-fat diet significantly improved adiposity and obesity-associated metabolic dysfunction, including glucose intolerance and insulin resistance, hyperlipidemia and hepatic steatosis, which were accompanied by increased whole-body energy expenditure. RNA sequencing analysis revealed extensive alterations in the transcriptome profiles associated with lipid metabolism and immune responses in adipose tissue of obese mice. Notably, TB treatment led to a significant reduction in ATM accumulation and a shift of the activation state of ATMs from the proinflammatory M1-like to the anti-inflammatory M2-like phenotype. Moreover, depletion of ATMs significantly abolished the TB-induced metabolic benefits.
Conclusions:
Our study demonstrates that TB at a low dose could increase energy expenditure and control ATM-mediated adipose inflammation in obese mice, thereby alleviating obesity and its associated metabolic dysfunction.
Insights
Talabostat (TB) reduces adipose tissue inflammation and improves metabolic dysfunction in obese mice. This drug works by decreasing pro-inflammatory macrophages, increasing energy expenditure, and alleviating obesity-related issues.
Area of Science:
- Immunology
- Metabolism
- Obesity Research
Background:
- Adipose tissue macrophages (ATMs) are key drivers of obesity-associated inflammation and metabolic dysfunction.
- Talabostat (TB) has shown therapeutic potential in tumors and obesity, but its specific mechanism in obesity-related inflammation is unclear.
Purpose of the Study:
- To investigate if the metabolic benefits of Talabostat (TB) in obesity are mediated by adipose tissue macrophage (ATM)-driven inflammation.
Main Methods:
- Male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks and treated daily with a low dose of TB (0.5 mg/kg).
- Metabolic parameters, adiposity, energy expenditure, and ATM profiles were assessed.
- RNA sequencing was performed on adipose tissue.
- ATM depletion was used to evaluate TB's mechanism of action.
Main Results:
- TB treatment significantly improved obesity-related metabolic dysfunction (glucose intolerance, insulin resistance, hyperlipidemia, hepatic steatosis) and increased energy expenditure.
- TB reduced ATM accumulation and shifted ATMs from a pro-inflammatory (M1-like) to an anti-inflammatory (M2-like) phenotype.
- Depletion of ATMs abolished the beneficial metabolic effects of TB.
Conclusions:
- Low-dose TB effectively increases energy expenditure and combats ATM-mediated adipose inflammation in obese mice.
- TB alleviates obesity and associated metabolic dysfunction by modulating ATM activity.
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