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

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 (NO 2 -OA), a regulator of metabolic and inflammatory signaling pa...

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Bibliographic Details
Published in:	Scientific reports Vol. 11; no. 1; p. 17788
Main Authors:	Manni, Michelle L., Heinrich, Victoria A., Buchan, Gregory J., O’Brien, James P., Uvalle, Crystal, Cechova, Veronika, Koudelka, Adolf, Ukani, Dharti, Rawas-Qalaji, Mohamad, Oury, Tim D., Hart, Renee, Ellgass, Madeline, Mullett, Steven J., Fajt, Merritt L., Wenzel, Sally E., Holguin, Fernando, Freeman, Bruce A., Wendell, Stacy G.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 07-09-2021 Nature Publishing Group Nature Portfolio
Subjects:	692/308 692/308/1426 692/699 692/699/1785 692/699/317 Adolescent Adult Allergens Allergic diseases Animal models Animal tissues Animals Anti-Asthmatic Agents - therapeutic use Antigens, Dermatophagoides - toxicity Asthma Asthma - drug therapy Asthma - etiology Asthma - metabolism Asthma - physiopathology Bile Bile acids Bile Acids and Salts - metabolism Body mass index Diet, High-Fat - adverse effects Drug Evaluation, Preclinical Fatty acids Fatty Acids - chemistry Fatty Acids - physiology Female Forced Expiratory Volume Glycocholic Acid - blood House dust Humanities and Social Sciences Humans Hypersensitivity Inflammation Liver - drug effects Liver - metabolism Lung - physiopathology Lung diseases Lungs Male Metabolism Mice Mice, Inbred C57BL Middle Aged multidisciplinary Nitro Compounds - therapeutic use Nitrogen dioxide Obesity Obesity - complications Obesity - metabolism Obesity - physiopathology Oleic acid Oleic Acids - therapeutic use Pathophysiology Respiratory function Respiratory Hypersensitivity - chemically induced Respiratory Hypersensitivity - drug therapy Respiratory Hypersensitivity - metabolism Respiratory tract diseases Science Science (multidisciplinary) Serum levels Thinness Ursodeoxycholic Acid - analogs & derivatives Ursodeoxycholic Acid - blood Vital Capacity Young Adult
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Summary:	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 (NO 2 -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 NO 2 -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. NO 2 -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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-021-96471-9