The Role Of Obesity On Airway Responsiveness And Pulmonary Inflammation In Mice

Part ⅠTHE ROLE OF OBESITY INDUCED BY HIGH-FAT DIETON PULMONARY INFLAMMATION AND FUNCTION INMICEObjective: Study the role of obesity induced by high-fat diet onpulmonary inflammation and function in ICR mice.Methods: After the mice were weaned, the tested group were offeredwith high-fat diet until postnatal day150(P150), the matched group wereoffered with standard-chow diets. Mice in hig h-fat group with weight10%-20%of heaiver than the matched group classified as over-weight group;Mice in high-fat group with weight>20%of heaiver than the matched groupwas classified as obese group. The basis value of pulmonary function wasrecorded, H&E staining and F4/80immunohistochmistry were performed tomeasure lung inflammation.Results:(1) H&E staining and F4/80immunohistochmistry of lungsindicated that inflammatory cells of obese group infiltration around bronchus, alveolar interval were more than over-weight group and matchedgroup, which were given priority to macrophages.(2) Pulmonary function(PIF, PEF, EF50) of obese group showed no statistical differences comparedwith over-weight group and matched group (P>0.05).Conclusions: Obesity could lead to pulmonary inflammation, but didnot alter airway ventilation function. Part ⅡTHE ROLE OF OBESITY INDUCED BY NEONATALOVERFEEDING ON AIRWAY RESPONSIVENESS ANDINFLAMMATION IN MICEObjective: Investigate the role of neonatal overfeeding on airwayresponsiveness and inflammation in mice.Methods: The neonatal overfeeding group was adjusted to three malemice per litter (Small Litter, SL), the matched group was adjusted to tenmale mice per litter (Normal Litter，NL) on postnatal day3(P3). On P21, allmice were offered with normal diet until P150. Airway responsiveness wasmeasured either on P21or P150, total and classified inflammatory cells inbronchoalveolar lavage fluid (BALF) were calculated. Lung inflammatory changes were assessed by hematoxylin&eosin (H&E) staining and F4/80immunohistochmistry; pulmonary collagen fibers were assessed by dyeingwith Masson and α-SAM immunohistochmistry. The level of leptin in serumwas measured by RIA; the level of TNF-in serum and BALF were testedby ELISA; TNF-, CTGF and TGF-β1mRNA in lung were quantifiedthrough real-time PCR.Results: Compared with NL group, SL group displayed increasedweight, impaired glucose tolerance and hyperleptinemia on P150. SL groupdisplayed enhanced airway responsiveness on P150, however which was notfound in SL group on P21. SL group appeared lung inflammation on P150,mainly characterized by inflammatory cells (macrophages) around thebronchi and alveoli interval. The levle of TNF-α in BALF and serum wereincreased markedly in SL mice on P150. Meanwhile, collagen fibers aroundthe bronchi in SL group were increased on P150; the expression of TGF-β1and CTGF mRNA in lungs were increased in SL group.Conclusions: In addition to resulting in a variety of metabolic changes,neonatal overfeeding could increase pulmonary inflammation, airwayremodeling and responsiveness in adult stage.