Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/200880
Type: Artigo de periódico
Title: Metformin Attenuates The Exacerbation Of The Allergic Eosinophilic Inflammation In High Fat-diet-induced Obesity In Mice.
Author: Calixto, Marina Ciarallo
Lintomen, Letícia
André, Diana Majoli
Leiria, Luiz Osório
Ferreira, Danilo
Lellis-Santos, Camilo
Anhê, Gabriel Forato
Bordin, Silvana
Landgraf, Richardt Gama
Antunes, Edson
Abstract: A positive relationship between obesity and asthma has been well documented. The AMP-activated protein kinase (AMPK) activator metformin reverses obesity-associated insulin resistance (IR) and inhibits different types of inflammatory responses. This study aimed to evaluate the effects of metformin on the exacerbation of allergic eosinophilic inflammation in obese mice. Male C57BL6/J mice were fed for 10 weeks with high-fat diet (HFD) to induce obesity. The cell infiltration and inflammatory markers in bronchoalveolar lavage (BAL) fluid and lung tissue were evaluated at 48 h after ovalbumin (OVA) challenge. HFD obese mice displayed peripheral IR that was fully reversed by metformin (300 mg/kg/day, two weeks). OVA-challenge resulted in higher influx of total cell and eosinophils in lung tissue of obese mice compared with lean group. As opposed, the cell number in BAL fluid of obese mice was reduced compared with lean group. Metformin significantly reduced the tissue eosinophil infiltration and prevented the reduction of cell counts in BAL fluid. In obese mice, greater levels of eotaxin, TNF-α and NOx, together with increased iNOS protein expression were observed, all of which were normalized by metformin. In addition, metformin nearly abrogated the binding of NF-κB subunit p65 to the iNOS promoter gene in lung tissue of obese mice. Lower levels of phosphorylated AMPK and its downstream target acetyl CoA carboxylase (ACC) were found in lung tissue of obese mice, which were restored by metformin. In separate experiments, the selective iNOS inhibitor aminoguanidine (20 mg/kg, 3 weeks) and the anti-TNF-α mAb (2 mg/kg) significantly attenuated the aggravation of eosinophilic inflammation in obese mice. In conclusion, metformin inhibits the TNF-α-induced inflammatory signaling and NF-κB-mediated iNOS expression in lung tissue of obese mice. Metformin may be a good pharmacological strategy to control the asthma exacerbation in obese individuals.
Subject: Amp-activated Protein Kinases
Animals
Asthma
Blotting, Western
Bronchoalveolar Lavage Fluid
Diet, High-fat
Enzyme Inhibitors
Eosinophils
Guanidines
Hypoglycemic Agents
Inflammation
Insulin Resistance
Lung
Male
Metformin
Mice
Mice, Inbred C57bl
Nitric Oxide
Nitric Oxide Synthase Type Ii
Obesity
Ovalbumin
Promoter Regions, Genetic
Protein Binding
Transcription Factor Rela
Tumor Necrosis Factor-alpha
Rights: aberto
Identifier DOI: 10.1371/journal.pone.0076786
Address: http://www.ncbi.nlm.nih.gov/pubmed/24204674
Date Issue: 2013
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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