Epigallocatechin-3-gallate protects against the exacerbation of allergic eosinophilic inflammation associated with obesity in mice.

Obesity is linked to worse asthma symptoms. Epigallocatechin-3-gallate (EGCG) reduces airway inflammation, but no study investigated the effects of EGCG on obesity-associated asthma. We aimed here to evaluate the effects of EGCG on allergen-induced airway inflammation in high-fat diet-fed mice. Male C57Bl/6 mice maintained on either standard-chow or high-fat diet for 12 weeks were treated or not with EGCG (10 mg/kg/day, gavage, two weeks). Animals were intranasally challenged with ovalbumin (OVA). In lung tissue and bronchoalveolar lavage fluid (BALF), cell counting and markers of inflammation and oxidative stress were evaluated. High-fat diet-fed mice exhibited significantly higher body weight and epididymal fat mass compared with lean group. EGCG treatment reduced by 20% the epididymal fat mass in obese mice (P < 0.05). The OVA-induced increases of total cells and eosinophils in lung tissue of obese mice were significantly reduced EGCG treatment. The increased levels of TNF-α, IL-4, IL-5 and eotaxin in BALF of obese mice were normalized by EGCG. Likewise, the enhanced expression of inducible nitric oxide synthase (iNOS) and nitric oxide metabolite (NOx) levels in obese mice were normalized by EGCG. Reactive­oxygen species (ROS) and superoxide dismutase (SOD) levels were elevated and reduced, respectively, in lung tissue of obese mice, both of which were restored by EGCG. In lean mice, EGCG had no significant effect in evaluated parameter (body measures, and inflammatory and oxidative markers). EGCG turns to normal the levels of inflammatory and oxidative stress markers in lungs of obese mice, suggesting it could be an option to attenuate obesity-related asthma.

Therapy with resveratrol attenuates obesity-associated allergic airway inflammation in mice.

Obesity and insulin resistance have been associated with deterioration in asthma outcomes. High oxidative stress and deficient activation of AMP-activated protein kinase (AMPK) have emerged as important regulators linking insulin resistance and inflammation. This study aimed to evaluate the effects of resveratrol on obesity-associated allergic pulmonary inflammation. Male C57/Bl6 mice fed with high-fat diet to induce obesity (obese group) or standard-chow diet (lean group) were treated or not with resveratrol (100mg/kg/day, two weeks). Mice were sensitized and challenged with ovalbumin (OVA). At 48h thereafter, bronchoalveolar lavage fluid was performed, and lungs collected for morphological studies and Western blot analysis. Treatment of obese mice with resveratrol significantly reduced hyperglycemia and insulin resistance, as well as the body measures (body mass, fat mass, % fat, and body area). OVA-challenge promoted a higher increase in pulmonary eosinophil infiltration in obese compared with lean mice, which was nearly abrogated by resveratrol treatment. Resveratrol markedly increased the phosphorylated AMPK expression in lung tissues of obese compared with lean mice. Resveratrol reduced the p47phox expression and reactive-oxygen species (ROS) production, and elevated the superoxide dismutase (SOD) levels in lung tissues of obese mice. The increased pulmonary levels of TNF-α and inducible nitric oxide synthase (iNOS) in obese mice were also normalized after resveratrol treatment. In lean mice, resveratrol failed to affect the levels of fasting glucose, p47phox, ROS levels, TNF-α, iNOS and phosphorylated AMPK. Resveratrol exhibits protective effects in obesity-associated lung inflammation that is accompanied by local AMPK activation and antioxidant property.