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Published on: June 23, 2013
Oleanolic Acid Improves Obesity-Related Inflammation and Insulin Resistance by Regulating Macrophages Activation
Wanqing Li1, Hongxiang Zeng1, Min Xu1
1Institute of Life Sciences, Chongqing Medical University, Chongqing, China.
Abstract:
The chronic low-grade inflammation of adipose tissues, primarily mediated by adipose tissue macrophages (ATMs), is the key pathogenic link between obesity and metabolic disorders. Oleanolic acid (OA) is a natural triterpenoid possessing anti-diabetic and anti-inflammation effects, but the machinery is poorly understood. This study investigated the detailed mechanisms of OA on adipose tissue inflammation in obese mice. C57BL/6J mice were fed with high-fat diet (HFD) for 12 weeks, then daily intragastric administrated with vehicle, 25 and 50 mg/kg OA for 4 weeks. Comparing with vehicle, OA administration in obese mice greatly improved insulin resistance, and reduced adipose tissue hypertrophy, ATM infiltration as well as the M1/M2 ratio. The pro-inflammatory markers were significantly down-regulated by OA in both adipose tissue of obese mice and RAW264.7 macrophages treated with interferon gamma/lipopolysaccharide (IFN-γ/LPS). Furthermore, it was found that OA suppressed activation of mitogen-activated protein kinase (MAPK) signaling and NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome through decreasing voltage dependent anion channels (VDAC) expression and reactive oxygen species (ROS) production. This is the first report that oleanolic acid exerts its benefits by affecting mitochondrial function and macrophage activation.
Insights
Oleanolic acid (OA) combats obesity-related inflammation by improving insulin resistance and reducing macrophage infiltration in adipose tissue. It achieves this by modulating mitochondrial function and suppressing key inflammatory pathways.
Area of Science:
- Metabolic disorders
- Obesity and inflammation
- Adipose tissue biology
Background:
- Chronic low-grade adipose tissue inflammation, driven by adipose tissue macrophages (ATMs), links obesity to metabolic disorders.
- Oleanolic acid (OA), a natural triterpenoid, shows anti-diabetic and anti-inflammatory potential, but its precise mechanisms remain unclear.
Purpose of the Study:
- To elucidate the detailed mechanisms by which Oleanolic acid (OA) mitigates adipose tissue inflammation in diet-induced obese mice.
Main Methods:
- Obese C57BL/6J mice (12-week high-fat diet) were treated with Oleanolic acid (25 and 50 mg/kg) or vehicle for 4 weeks.
- Evaluated insulin resistance, adipose tissue hypertrophy, ATM infiltration, M1/M2 macrophage polarization, pro-inflammatory markers, MAPK signaling, and NLRP3 inflammasome activation.
- Assessed the impact of OA on mitochondrial function, including voltage-dependent anion channel (VDAC) expression and reactive oxygen species (ROS) production in adipose tissue and RAW264.7 macrophages.
Main Results:
- Oleanolic acid treatment significantly improved insulin resistance, reduced adipose tissue hypertrophy, and decreased ATM infiltration and the M1/M2 ratio in obese mice.
- OA administration markedly down-regulated pro-inflammatory markers in both adipose tissue and lipopolysaccharide/interferon-gamma-stimulated macrophages.
- OA suppressed MAPK signaling and NLRP3 inflammasome activation by reducing VDAC expression and ROS production, indicating improved mitochondrial function.
Conclusions:
- Oleanolic acid effectively ameliorates adipose tissue inflammation and insulin resistance in obesity.
- OA exerts its beneficial effects by targeting mitochondrial dysfunction and modulating macrophage activation pathways.
- This study provides novel insights into the molecular mechanisms underlying OA's anti-inflammatory and anti-diabetic properties.
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