Nitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma

Abstract Bile acid profiles are altered in obese individuals with asthma. Thus, we sought to better understand how obesity-related systemic changes contribute to lung pathophysiology. We also test the therapeutic potential of nitro-oleic acid (NO2-OA), a regulator of metabolic and inflammatory signa...

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Autores principales: Michelle L. Manni, Victoria A. Heinrich, Gregory J. Buchan, James P. O’Brien, Crystal Uvalle, Veronika Cechova, Adolf Koudelka, Dharti Ukani, Mohamad Rawas-Qalaji, Tim D. Oury, Renee Hart, Madeline Ellgass, Steven J. Mullett, Merritt L. Fajt, Sally E. Wenzel, Fernando Holguin, Bruce A. Freeman, Stacy G. Wendell
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/40111bfc71bc4fc1b5f339c0101d5c5d
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spelling oai:doaj.org-article:40111bfc71bc4fc1b5f339c0101d5c5d2021-12-02T19:12:35ZNitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma10.1038/s41598-021-96471-92045-2322https://doaj.org/article/40111bfc71bc4fc1b5f339c0101d5c5d2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96471-9https://doaj.org/toc/2045-2322Abstract Bile acid profiles are altered in obese individuals with asthma. Thus, we sought to better understand how obesity-related systemic changes contribute to lung pathophysiology. We also test the therapeutic potential of nitro-oleic acid (NO2-OA), a regulator of metabolic and inflammatory signaling pathways, to mitigate allergen and obesity-induced lung function decline in a murine model of asthma. Bile acids were measured in the plasma of healthy subjects and individuals with asthma and serum and lung tissue of mice with and without allergic airway disease (AAD). Lung function, indices of inflammation and hepatic bile acid enzyme expression were measured in obese mice with house dust mite-induced AAD treated with vehicle or NO2-OA. Serum levels of glycocholic acid and glycoursodeoxycholic acid clinically correlate with body mass index and airway hyperreactivity whereas murine levels of β-muricholic acid and tauro-β-muricholic acid were significantly increased and positively correlated with impaired lung function in obese mice with AAD. NO2-OA reduced murine bile acid levels by modulating hepatic expression of bile acid synthesis enzymes, with a concomitant reduction in small airway resistance and tissue elastance. Bile acids correlate to body mass index and lung function decline and the signaling actions of nitroalkenes can limit AAD by modulating bile acid metabolism, revealing a potential pharmacologic approach to improving the current standard of care.Michelle L. ManniVictoria A. HeinrichGregory J. BuchanJames P. O’BrienCrystal UvalleVeronika CechovaAdolf KoudelkaDharti UkaniMohamad Rawas-QalajiTim D. OuryRenee HartMadeline EllgassSteven J. MullettMerritt L. FajtSally E. WenzelFernando HolguinBruce A. FreemanStacy G. WendellNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Michelle L. Manni
Victoria A. Heinrich
Gregory J. Buchan
James P. O’Brien
Crystal Uvalle
Veronika Cechova
Adolf Koudelka
Dharti Ukani
Mohamad Rawas-Qalaji
Tim D. Oury
Renee Hart
Madeline Ellgass
Steven J. Mullett
Merritt L. Fajt
Sally E. Wenzel
Fernando Holguin
Bruce A. Freeman
Stacy G. Wendell
Nitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma
description Abstract Bile acid profiles are altered in obese individuals with asthma. Thus, we sought to better understand how obesity-related systemic changes contribute to lung pathophysiology. We also test the therapeutic potential of nitro-oleic acid (NO2-OA), a regulator of metabolic and inflammatory signaling pathways, to mitigate allergen and obesity-induced lung function decline in a murine model of asthma. Bile acids were measured in the plasma of healthy subjects and individuals with asthma and serum and lung tissue of mice with and without allergic airway disease (AAD). Lung function, indices of inflammation and hepatic bile acid enzyme expression were measured in obese mice with house dust mite-induced AAD treated with vehicle or NO2-OA. Serum levels of glycocholic acid and glycoursodeoxycholic acid clinically correlate with body mass index and airway hyperreactivity whereas murine levels of β-muricholic acid and tauro-β-muricholic acid were significantly increased and positively correlated with impaired lung function in obese mice with AAD. NO2-OA reduced murine bile acid levels by modulating hepatic expression of bile acid synthesis enzymes, with a concomitant reduction in small airway resistance and tissue elastance. Bile acids correlate to body mass index and lung function decline and the signaling actions of nitroalkenes can limit AAD by modulating bile acid metabolism, revealing a potential pharmacologic approach to improving the current standard of care.
format article
author Michelle L. Manni
Victoria A. Heinrich
Gregory J. Buchan
James P. O’Brien
Crystal Uvalle
Veronika Cechova
Adolf Koudelka
Dharti Ukani
Mohamad Rawas-Qalaji
Tim D. Oury
Renee Hart
Madeline Ellgass
Steven J. Mullett
Merritt L. Fajt
Sally E. Wenzel
Fernando Holguin
Bruce A. Freeman
Stacy G. Wendell
author_facet Michelle L. Manni
Victoria A. Heinrich
Gregory J. Buchan
James P. O’Brien
Crystal Uvalle
Veronika Cechova
Adolf Koudelka
Dharti Ukani
Mohamad Rawas-Qalaji
Tim D. Oury
Renee Hart
Madeline Ellgass
Steven J. Mullett
Merritt L. Fajt
Sally E. Wenzel
Fernando Holguin
Bruce A. Freeman
Stacy G. Wendell
author_sort Michelle L. Manni
title Nitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma
title_short Nitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma
title_full Nitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma
title_fullStr Nitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma
title_full_unstemmed Nitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma
title_sort nitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/40111bfc71bc4fc1b5f339c0101d5c5d
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