Metabolic shift favoring C18:0 ceramide accumulation in obese asthma

Choi, Youngwoo; Kim, Minji; Kim, Su Jung; Yoo, Hyunju; Kim, Seung Hyun; Park, Hae‐Sim

doi:10.1111/all.14366

Cited by 23 publications

(17 citation statements)

References 53 publications

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“…Increased ceramide levels may also contribute to the development of obese asthma. Choi et al 91 found multiple ceramides (C16:0, C18:0, and C20:0) to accumulate in obese mice as a result of a high‐fat diet, inducing AHR and inflammation. Increased expression of ceramide synthase (CerS) 1 and CerS6 was found in the lungs, and CerS6 was identified as a potential future therapeutic target for obese asthma.…”

Section: Molecular Mechanisms In the Development Of Asthmamentioning

confidence: 99%

Advances and recent developments in asthma in 2020

Cevhertas

Öğülür

Maurer

et al. 2020

Allergy

126

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In this review, we discuss recent publications on asthma and review the studies that have reported on the different aspects of the prevalence, risk factors and prevention, mechanisms, diagnosis, and treatment of asthma. Many risk and protective factors and molecular mechanisms are involved in the development of asthma. Emerging concepts and challenges in implementing the exposome paradigm and its application in allergic diseases and asthma are reviewed, including genetic and epigenetic factors, microbial dysbiosis, and environmental exposure, particularly to indoor and outdoor substances. The most relevant experimental studies further advancing the understanding of molecular and immune mechanisms with potential new targets for the development of therapeutics are discussed. A reliable diagnosis of asthma, disease endotyping, and monitoring its severity are of great importance in the management of asthma. Correct evaluation and management of asthma comorbidity/ multimorbidity, including interaction with asthma phenotypes and its value for the precision medicine approach and validation of predictive biomarkers, are further detailed. Novel approaches and strategies in asthma treatment linked to mechanisms and endotypes of asthma, particularly biologicals, are critically appraised. Finally, due to the recent pandemics and its impact on patient management, we discuss the challenges, relationships, and molecular mechanisms between asthma, allergies, SARS-CoV-2, and COVID-19.

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Section: Molecular Mechanisms In the Development Of Asthmamentioning

confidence: 99%

Advances and recent developments in asthma in 2020

Cevhertas

Öğülür

Maurer

et al. 2020

Allergy

126

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“…It is reported that SP‐B could suppress sPLA2 activity 49 . Alterations in C18:0 ceramide had a remarked association with M1 macrophage polarization in the high fat diet‐induced obese mice 50 . In addition, C18:0 ceramide expression has been reported significantly increased in the lower airway epithelium of the patients with cystic fibrosis 51 .…”

Section: Discussionmentioning

confidence: 98%

Down‐regulated surfactant protein B in obese asthmatics

Cao

Moon

Yoo

et al. 2022

Clin Experimental Allergy

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Background: Obesity is a common comorbid condition in adult asthmatics and known as a feature of asthma severity. However, the molecular mechanism under obesityinduced inflammation has not yet been fully understood.Objective: Considering the essential role of hydrophobic surfactant protein B (SP-B) in lung function, SP-B was targeted to examine its involvement in the development of obesity-induced airway inflammation in asthmatics. Methods:The aim was to examine an alteration in circulating SP-B according to obesity in adult asthmatics, 129 asthmatics were enrolled and classified into 3 groups (obese, overweight and normal-weight groups) according to body mass index (BMI).Circulating SP-B levels were determined by enzyme-linked immunosorbent assay.Four single nucleotide polymorphisms of SFTPB gene were genotyped. Serum ceramide levels were measured by liquid chromatography-tandem mass spectrometry.Results: Significantly lower serum SP-B levels were noted in the obese group than in the overweight or normal-weight group (p = .002). The serum SP-B level was significantly correlated with serum levels of C18:0 ceramide and transforming growth factor beta 1 as well as BMI (r = −0.200; r = −0.215; r = −0.332, p < .050 for all). An inverse correlation was noted between serum SP-B and fractional exhaled nitric oxide levels in female asthmatics (r = −0.287, p = .009). Genetic predisposition of the SFTPB gene at 9306 A>G to the obese and overweight groups was noted. Conclusion:Obesity altered ceramide metabolism leading to pulmonary surfactant dysfunction and impaired resolution of airway inflammation, finally contributing to the phenotypes of obese asthmatics.

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“…Among them, ceramide could contribute to airway hyperresponsiveness, suggesting a possible correlation with asthma severity [ 229 ]. Moreover, elevated levels of C18:0 and C:20 were found in the sera of obese asthmatics [ 230 ]. Although the exact mechanisms are not comprehended yet, clinical and experimental research have suggested the specific metabolic changes in obese asthma.…”

Section: Changes In Metabolite Profiles According To the Phenotype Of Asthmamentioning

confidence: 99%

Potential Metabolic Biomarkers in Adult Asthmatics

2021

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Asthma is the most common chronic airway inflammation, with multiple phenotypes caused by complicated interactions of genetic, epigenetic, and environmental factors. To date, various determinants have been suggested for asthma pathogenesis by a new technology termed omics, including genomics, transcriptomics, proteomics, and metabolomics. In particular, the systematic analysis of all metabolites in a biological system, such as carbohydrates, amino acids, and lipids, has helped identify a novel pathway related to complex diseases. These metabolites are involved in the regulation of hypermethylation, response to hypoxia, and immune reactions in the pathogenesis of asthma. Among them, lipid metabolism has been suggested to be related to lung dysfunction in mild-to-moderate asthma. Sphingolipid metabolites are an important mediator contributing to airway inflammation in obese asthma and aspirin-exacerbated respiratory disease. Although how these molecular variants impact the disease has not been completely determined, identification of new causative factors may possibly lead to more-personalized and precise pathway-specific approaches for better diagnosis and treatment of asthma. In this review, perspectives of metabolites related to asthma and clinical implications have been highlighted according to various phenotypes.

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Metabolic shift favoring C18:0 ceramide accumulation in obese asthma

Cited by 23 publications

References 53 publications

Advances and recent developments in asthma in 2020

Advances and recent developments in asthma in 2020

Down‐regulated surfactant protein B in obese asthmatics

Potential Metabolic Biomarkers in Adult Asthmatics

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