High-fat diet-induced obesity impairs insulin signaling in lungs of allergen-challenged mice: Improvement by resveratrol

André, Diana Majolli; Calixto, Marina C.; Sollon, Carolina; Alexandre, Eduardo C.; Tavares, Edith Bastos Gandra; Naime, Ana Carolina Antunes; Anhê, Gabriel Forato; Antunes, Edson

doi:10.1038/s41598-017-17558-w

Cited by 20 publications

(12 citation statements)

References 55 publications

(61 reference statements)

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“…Hyperglycaemia and insulin resistance are also suggested to be risk factors for asthma and lung fibrosis 19,20 . Previous studies have showed that obesity induce impairment of insulin signaling, which can lead to bronchoconstriction, fibrosis, and AHR 21,22 . Empagliflozin and dulaglutide restored the metabolic abnormality, including leptin and insulin levels, in this study model.…”

Section: Discussionmentioning

confidence: 99%

Empagliflozin and Dulaglutide are Effective against Obesity-induced Airway Hyperresponsiveness and Fibrosis in A Murine Model

Park

Han

et al. 2019

Sci Rep

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Patients with asthma with obesity experience severe symptoms, are unresponsive to conventional asthma treatment, and lack proper pharmacotherapy. Empagliflozin and dulaglutide, developed for diabetes, reduce weight, decrease insulin resistance, and exert additive effects. We evaluated the efficacy of empagliflozin, dulaglutide, and their combination on obesity-induced airway hyperresponsiveness (AHR) and lung fibrosis using a murine model. We assigned C57BL/6J mice to five groups: control, high-fat diet (HFD), and HFD with empagliflozin, dulaglutide, or both. Mice received a 12-week HFD, empagliflozin (5 days/week, oral gavage), and dulaglutide (once weekly, intraperitoneally). Both drugs significantly attenuated HFD-induced weight increase, abnormal glucose metabolism, and abnormal serum levels of leptin and insulin, and co-treatment was more effective. Both drugs significantly alleviated HFD-induced AHR, increased macrophages in bronchoalveolar lavage fluid (BALF), and co-treatment was more effective on AHR. HFD-induced lung fibrosis was decreased by both drugs alone and combined. HFD induced interleukin (IL)-17, transforming growth factor (TGF)-β1, and IL-1β mRNA and protein expression, which was significantly reduced by empagliflozin, dulaglutide, and their combination. Tumour necrosis factor (TNF)-α and IL-6 showed similar patterns without significant differences. HFD-enhanced T helper (Th) 1 and Th17 cell differentiation was improved by both drugs. Empagliflozin and dulaglutide could be a promising therapy for obesity-induced asthma and showed additive effects in combination.

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Section: Discussionmentioning

confidence: 99%

Empagliflozin and Dulaglutide are Effective against Obesity-induced Airway Hyperresponsiveness and Fibrosis in A Murine Model

Park

Han

et al. 2019

Sci Rep

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“…[ 59 ] observed that insulin suppresses cardiac muscle atrophy by Akt-dependent inhibition of FoxO3 in the skeletal muscle. In addition, insulin significantly increases Akt phosphorylation in the lung tissue of lean rats, but not in obese mice, indicating that this tissue does not respond to insulin after 12 weeks of HFD [ 60 ]. Additionally, Akt expression and activation in the mouse skin increases with age [ 61 ].…”

Section: Differential Roles Of Akt/foxos Axis In Metabolic- and Non-metabolic Organsmentioning

confidence: 99%

“…We previously reported that Akt-induced FoxO1 phosphorylation was reduced in the livers of aged rats, whereas it was increased in the kidney [ 65 ]. Different trends of changes in the Akt/FoxOs axis in metabolic and non-metabolic organs during aging are shown in Table 1 [ 31 , 32 , 60 - 62 , 66 - 73 ].…”

Section: Differential Roles Of Akt/foxos Axis In Metabolic- and Non-metabolic Organsmentioning

confidence: 99%

Organ-differential Roles of Akt/FoxOs Axis as a Key Metabolic Modulator during Aging

Kim

Bang

et al. 2021

Aging and disease

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FoxOs and their post-translational modification by phosphorylation, acetylation, and methylation can affect epigenetic modifications and promote the expression of downstream target genes. Therefore, they ultimately affect cellular and biological functions during aging or occurrence of age-related diseases including cancer, diabetes, and kidney diseases. As known for its key role in aging, FoxOs play various biological roles in the aging process by regulating reactive oxygen species, lipid accumulation, and inflammation. FoxOs regulated by PI3K/Akt pathway modulate the expression of various target genes encoding MnSOD, catalases, PPARγ, and IL-1β during aging, which are associated with age-related diseases. This review highlights the age-dependent differential regulatory mechanism of Akt/FoxOs axis in metabolic and non-metabolic organs. We demonstrated that age-dependent suppression of Akt increases the activity of FoxOs (Akt/FoxOs axis upregulation) in metabolic organs such as liver and muscle. This Akt/FoxOs axis could be modulated and reversed by antiaging paradigm calorie restriction (CR). In contrast, hyperinsulinemia-mediated PI3K/Akt activation inhibited FoxOs activity (Akt/FoxOs axis downregulation) leading to decrease of antioxidant genes expression in non-metabolic organs such as kidneys and lungs during aging. These phenomena are reversed by CR. The results of studies on the process of aging and CR indicate that the Akt/FoxOs axis plays a critical role in regulating metabolic homeostasis, redox stress, and inflammation in various organs during aging process. The benefical actions of CR on the Akt/FoxOs axis in metabolic and non-metabolic organs provide further insights into the molecular mechanisms of organ-differential roles of Akt/FoxOs axis during aging.

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“…Resveratrol also significantly increased the phosphorylated AMPK expression, reduced the expression of p47phox and TNF-α and prevented ROS production in lung tissues of obese mice ( Andre et al, 2016 ). Furthermore, another study demonstrated that resveratrol administration improved allergic airway inflammation and obesity-associated asthma exacerbations by restoring insulin-induced phosphorylation of Akt, insulin receptor substrate 1 (IRS-1) and insulin receptor β (IRβ), decreasing JNK and NF-κB signaling pathways in lung tissues of obese mice ( Andre et al, 2017 ).…”

Section: Resveratrol and Asthmamentioning

confidence: 99%

Resveratrol extracted from Chinese herbal medicines: A novel therapeutic strategy for lung diseases

2020

Chinese Herbal Medicines

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Lung diseases and their related complications represent a critical source of morbidity and mortality globally and have become a research focus in recent years. There are plenty of hazards that threaten the health of lung by exposure to external environmental stimuli, such as dust, cigarette smoke, PM2.5, air pollution and pathogen infection. These risks lead to the impairment of lung function and subsequent lung diseases including pneumonia, chronic obstructive pulmonary disease (COPD), asthma and idiopathic pulmonary fibrosis (IPF). Compared with antibiotics and corticosteroids therapies, traditional Chinese medicine prescriptions are more effective with fewer side effects. A considerable variety of bioactive ingredients have been extracted and identified from Chinese herbal medicines and are used for the treatment of different lung diseases, including resveratrol. Increasing studies have reported promising therapeutic effects of resveratrol against lung diseases by inhibiting oxidative stress, inflammation, aging, fibrosis and cancer both in vitro and in vivo . In this review, the recent progress in the studies of lung-protective effects and underlying mechanisms of resveratrol and also highlight the potency of resveratrol and traditional Chinese prescriptions containing resveratrol as promising therapeutic options were summarized for the treatment of lung and respiratory diseases.

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High-fat diet-induced obesity impairs insulin signaling in lungs of allergen-challenged mice: Improvement by resveratrol

Cited by 20 publications

References 55 publications

Empagliflozin and Dulaglutide are Effective against Obesity-induced Airway Hyperresponsiveness and Fibrosis in A Murine Model

Empagliflozin and Dulaglutide are Effective against Obesity-induced Airway Hyperresponsiveness and Fibrosis in A Murine Model

Organ-differential Roles of Akt/FoxOs Axis as a Key Metabolic Modulator during Aging

Resveratrol extracted from Chinese herbal medicines: A novel therapeutic strategy for lung diseases

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