title: Treatment of obese asthma in a mouse model by simvastatin is associated with improving dyslipidemia and decreasing leptin level.
abstract: Obesity can cause or worsen asthma. Compared with common asthma, obese asthma is difficult to control. Statins are effective serum cholesterol-lowering agents in clinical practice, and they also have anti-inflammatory properties, which in theory are potentially beneficial in asthma. Many studies have shown that simvastatin has good therapeutic effect in animal models of asthma. However, the therapeutic effect and action mechanism of simvastatin for obese asthma remain unclear. Leptin, a satiety hormone, is in positive correlation with total body fat mass and may also play a significant role in the pathogenesis of asthma. In this study, we use the method of high-fat diet and ovalbumin (OVA) sensitization and challenge to establish the mouse model of obesity and asthma, and find that obese asthmatic mice has higher levels of glucose, lipid and leptin in serum, and neutrophil percentage in bronchoalveolar lavage fluid (BALF), and more severe airway inflammation and structural changes in lung tissues than non-obese asthmatic mice, and respond poorly to dexamethasone treatment, which indicates that obese asthma might belong to steroid-resistant (SR) asthma. Simvastatin treatment reduces the levels of glucose, lipid, leptin and neutrophil percentage, and improves airway inflammation and remodeling, which can be as a potential therapeutic target used in the treatment of obese asthma in humans. Correlation analysis shows that there is positive correlation between neutrophil percentage and serum leptin/cholesterol level, which indicates that the therapeutic efficacy of simvastatin on obese asthma might be associated with improving dyslipidemia and decreasing leptin level.
authors.affiliation: Department of Pulmonary Medicine, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, 266011, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Pulmonary Medicine, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, 266011, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pulmonary Medicine, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, 266011, China.
authors.forename: Huaping
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Anesthesia, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, 266011, China. Electronic address: slixin1230@126.com.
authors.forename: Lixin
authors.initials: L
authors.lastname: Sun
mesh_terms: D000818:Animals; D001249:Asthma / Q000150:complications / Q000188:drug therapy*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy*; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D020738:Leptin / Q000097:blood*; D007958:Leukocyte Count; D008055:Lipids / Q000097:blood; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications*; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020738:Leptin; D008055:Lipids; D019821:Simvastatin
keywords: Asthma; Dexamethasone; Leptin; Obesity; Simvastatin