The Effect Of Obesity On Airway Inflammation And Remodeling, And Its Potential Mechanism

PARTI Maternal High-Fat Diet Feeding During Pregnancy And Lactation Augments Lung Inflammation And Remodeling In The OffspringObject:Accumulating evidence suggests that maternal obesity increases the risk of their offspring developing noncommunicable diseases later in life, but the potential mechanisms, especially those resulting in abnormal respiratory conditions, are not thoroughly understood. Here, we used maternal high-fat diet (HFD) feeding during premating, pregnancy, and lactation to investigate the effect of maternal HFD on offspring lung development.Methods:Offspring birth weight and body weight and composition were measured. Serum leptin levels were measured by ELISA. Hematoxylin-eosin (H&E) and Masson's staining were used in paraffin-embedded lung sections. Levels of transfer growth factor-(TGF-) and-smooth muscle actin (-SMA) were examined by immunohistochemistry and western blot, respectively.Results:Maternal HFD feeding during pregnancy and lactation lead to higher birth weight, final body weight, fat accumulation and hyperleptinemia in offspring. Maternal HFD feeding aggravated lung inflammatory response in the offspring, resulting in inflammatory cell infiltration and collagen deposition potentially via the enhanced expression of TGF-? and a-SMA in the offspring.Conclusions:Maternal HFD exposure in utero and during the lactation period could induce a remarkable inflammatory cell recruitment effect in the offspring lung and promote lung tissue remodeling.PART II Leptin Inhibits Airway Hyperresponsiveness In An Ovalbumin-Induced Mouse Model Of Allergic AsthmaObjectives:Epidemiologic data indicate that the prevalence and incidence of asthma have increased among the obese population; however, the literature regarding the role of obesity in asthmatic symptoms is inconsistent. This study aims to explore the role of anorexigenic peptide, leptin, in the modulation of airway inflammation and responsiveness.Methods:ICR mice were sensitized with ovalbumin (OVA) and then intraperitoneally injected with recombinant mouse leptin daily for 7 days. Airway resistance was measured by whole-body plethysmography, and the number of total cells and inflammatory cells in bronchoalveolar lavage fluids was counted. Hematoxylin-eosin staining was used to measure the pathological changes in the lung. Enzyme-linked immunosorbent assay was implemented to measure the serum leptin levels. Real-time polymerase chain reaction and western blotting were used to evaluate the transcriptional and translational level of para-/sympathetic nerve receptors.Results:Serum leptin concentrations did not increase, even after application of exogenous leptin; however, leptin infusion significantly increased the total and inflammatory cell number of bronchoalveolar lavage fluids in OVA sensitized mice. Treatment with leptin attenuated OVA- induced airway responsiveness. Transcriptional expression of the leptin and muscarinic acetylcholine receptors decreased in lung tissue, but transcript and protein levels of adrenergic beta-2 receptor (Adrb2) increased after leptin treatment. More importantly, leptin administration reduced expression of OVA-induced smooth muscle actin alpha.Conclusions:Leptin may attenuate allergen-induced airway reactivity by increasing Adrb2 expression, even though leptin is thought to be an adipocyte-derived pro-inflammatory cytokine.