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

• 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
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-96471-9

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.