The Effect Of Obesity And Dietary Restriction On The Development Of Asthma And Its Potential Mechanism

THE EFFECT OF OBESITY ON PULMONARYINFLAMMATION AND AIRWAY REMODELING INOB/OB MICEObject：Explore the effect of obesity on the pulmonary inflammationand airway remodeling in ob/ob mice.Methods: Ob/ob gene knockout C57BL/6j male mice buy fromBeijing as obese group, the wild type of C57male mice as normal group.Hematoxylin eosin staining was to observe the effect of obesity onpulmonary inflammation; the immunohistochemical of α-SMA and massonstaining was to detect the effect of obesity on the lung tissue remodeling.Results: Ob/ob gene knockout induced obesity model, HE staining forlung tissue inflammation and quantitative of inflammation cells, the result isthat inflammation cells around the bronchial in obese mice increasedsignificantly than the normal group, but there is no obvious difference aboutthe inflammatory cells surrounding alveolar; the lung tissueimmunohistochemical of alpha SMA in obese mice and quantitative average optical density value, results show that the expression of smooth musclemovement protein around bronchial was positive; Masson staining andanalysis average optical density value found that collagen depositionobviously around bronchus in obese mice, but there is no obvious changearound alveolar.Conclusions: Ob/ob gene knock out induced obesity can increase theinfiltration of inflammation in pulmonary and promote remodeling. OBESITY INDUCED BY NEONATAL OVERFEEDINGWORSE THE PULMONARY INFLAMMATION ANDAIRWAY RESPONSIVENESSObjective: To explore the effect of neonatal overfeeding caused obesityon airway inflammation and responsiveness in asthma mice.Methods: Neonatal overfeeding induced obesity model was establishedby reducing the litter size. Asthma model was founded by sensitized andchallenged with ovalbumin intraperitoneal injection and aerosol respectively,control group were treated with saline instead. The groups were defined asobese asthma group, asthma group, obese group, control group. Airwayresistance was performed after the last OVA stimulation to detect the effect of obesity on airway responsiveness. To identify the role of obesity onairway inflammation, bronchoalveolar lavage and lung tissuehematoxylin-eosin stain (H&E) were implemented.Results:(1) Airway responsiveness in asthmatic mice was higher thanthat in controls,and obese asthma mice showed a greater degree of airwayresponsiveness, when compared with obese mice and control mice(P＜0.05).(2) Total and classified cells in BALF of obese asthma mice revealed amark able increase than that of obese mice and asthma mice (P＜0.05).Except for the total cells and macrophages displayed a significant differencebetween obese mice and controls (P＜0.05), there was no other difference incell count between these two groups（P>0.05）.(3) Hematoxylin-Eosin stainindicated that inflammatory cells recruit to the peri-bronchial and interstitialalveolar obviously in obese asthma mice than that in obese mice (P＜0.05),but obese asthma mice just exhibited more cell accumulation inperibronchial when compared with asthma mice.Conclusion: Neonatal overfeeding induced obesity can augment theairway inflammation and responsiveness in asthma mice. THE ROLE OF WEIGHT-LOSS INDUCED BY DIETARYRESTRICTION ON THE PULMONARY INFLAMMATIONAND AIRWAY HYPERRESPONSIVENESS ANDREMODELING IN OBESE MICEObjective: To understand the mechanism about the effect of obesity onasthma, we establish the weight-loss mice model by dietary restriction toview whether weight-loss can change the pulmonary inflammation, airwayhyperresponsiveness and airway remodeling resulted by obesity.Methods: To establish the obese mice model induced by neonataloverfeeding reducing litters size. The obese group was adjusted to three miceper litter, the normal group mice (NL) was adjusted to11mice per litter in3days after birth. Wean and drink the water after three weeks of breastfeeding.From35days, weigh the food weight that the daily food intake of every micefor10days, obese mice can be divided into free diet intake group (SL/AL)and dietary restrictions (SL/F R) mice since45th day, food intake of SL/F Ris only two-thirds of the average daily food intake of mice, until150days.Detection the responsiveness of mice to acetyl choline, harvest the bloodfrom the eyeball and detect the cytokines VEGF, TGF-β1, TNF-α, IL-6, IL-10, leptin and insulin of the serum. Then get the alveolar lavage fluid andcount the total and classified of inflammation cells and detect the cytokinesof TGF-beta1and IL-10; He staining, masson staining, theimmunohistochemical of α-SMA, the gene expression of TGF-β1, CTGF,VEGF, IL-10, TNF-α and IL–6, the protein expression of MMP9were used to examine the degree of lung tissue inflammation and remodeling.Results: A moderate food restriction significantly reduced body weightand improved hyperinsulinemia and glucose intolerance in SL mice. SL/ALmice displayed high airway responsiveness to methacholine, which wasattenuated by FR. Additionally, SL/FR mice displayed fewer infiltratedinflammatory cells around the alveolar, accompanied by reduced levels ofIL-6and leptin compared with SL/AL mice, but there is no obvious effect onthe expression of TNF-α and the inflammatory cells around bronchus and.Surprisingly, the anti-inflammatory levels of IL-10and T regulatory cells(Treg) were elevated in SL/AL mice, and were reduced in SL/FR mice.Finally, we observed an obvious collagen accumulation around the bronchus,and the remodeling related cytokine and protein levels of VEGF, CTGF andMMP-9were elevated in the SL/AL mice, which was attenuated by FR, butthere is no effct on the expression of TGF-β1,.Concludes: Our data suggested that food restriction not only improves avariety of metabolic defects induced by neonatal overfeeding, but alsoabolishes partly the airway hyperresponsiveness, inflammation andremodeling induced by obesity.