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.

• MeSH
• Anti-Asthmatic Agents therapeutic use   MeSH
• Antigens, Dermatophagoides toxicity   MeSH
• Asthma drug therapy   etiology   metabolism   physiopathology   MeSH
• Diet, High-Fat adverse effects   MeSH
• Adult MeSH
• Nitro Compounds therapeutic use   MeSH
• Thinness MeSH
• Liver drug effects   metabolism   MeSH
• Glycocholic Acid blood   MeSH
• Ursodeoxycholic Acid analogs & derivatives   blood   MeSH
• Oleic Acids therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Fatty Acids chemistry   physiology   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Obesity complications   metabolism   physiopathology   MeSH
• Lung physiopathology   MeSH
• Drug Evaluation, Preclinical MeSH
• Respiratory Hypersensitivity chemically induced   drug therapy   metabolism   MeSH
• Forced Expiratory Volume MeSH
• Vital Capacity MeSH
• Bile Acids and Salts metabolism   MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Anti-Asthmatic Agents MeSH
• Antigens, Dermatophagoides MeSH
• CXA-10 MeSH Browser
• Nitro Compounds MeSH
• glycoursodeoxycholic acid MeSH Browser
• Glycocholic Acid MeSH
• Ursodeoxycholic Acid MeSH
• Oleic Acids MeSH
• Fatty Acids MeSH
• Bile Acids and Salts MeSH