Maternal Obesity in Mice Exacerbates the Allergic Inflammatory Response in the Airways of Male Offspring

Abstract

It was previously demonstrated that non-allergen-sensitized rodents born to mothers exposed to a high-fat diet (HFD) spontaneously develop lower respiratory compliance and higher respiratory resistance. In the present study, we sought to determine if mice born to mothers consuming HFD would exhibit changes in inflammatory response and lung remodeling when subjected to ovalbumin (OVA) sensitization/challenge in adult life. Mice born to dams consuming either HFD or standard chow had increased bronchoalveolar lavage (BAL) levels of IL-1β, IL-4, IL-5, IL-10, IL-13, TNF-α and TGF-β1 after challenge with OVA. IL-4, IL-13, TNF-α and TGF-β1 levels were further increased in the offspring of HFD-fed mothers. Mice born to obese dams also had exacerbated values of leukocyte infiltration in lung parenchyma, eosinophil and neutrophil counts in BAL, mucus overproduction and collagen deposition. The programming induced by maternal obesity was accompanied by increased expression of miR-155 in peripheral-blood mononuclear cells and reduced miR-133b in trachea and lung tissue in adult life. Altogether, the present data support the unprecedented notion that the progeny of obese mice display exacerbated responses to sensitization/challenge with OVA, leading to the intensification of the morphological changes of lung remodeling. Such changes are likely to result from long-lasting changes in miR-155 and miR-133b expression. 13 of 23 HFD/OVA mice (respectively, 172% and 177% higher than in SC/SHAM and HFD/SHAM; p = 0.006 and p < 0.0001). In contrast to IL-1β, the level of TNF-α in BAL of HFD/OVA was higher than in those of SC/OVA (86% higher; p = 0.0008) (p = 0.01 for interaction) (Figure 6b).

Maternal Obesity and Kawasaki Disease-like Vasculitis: A New Perspective on Cardiovascular Injury and Inflammatory Response in Offspring Male Mice

“…In the first stage of the KD pathological process, neutrophil-dominated immune cells mediate necrotizing vasculitis leading to full-thickness damage to the vessel wall [15,18]. Furthermore, animal study has demonstrated that maternal obesity exacerbated the infiltration of neutrophil in inflammatory response in the airways of male offspring [46]. Collectively, our findings suggest that maternal obesity may affect the long-term immune response and exacerbate KD-like vasculitis in male offspring mice through G-CSF.…”

Allergic Diseases and Childhood Obesity: A Detrimental Link?

“…The higher risk of allergic reactions in children of obese mothers seems to depend on the increased production of inflammatory cytokines induced by excess adipose tissue. Such changes are likely to result from long-lasting changes in miR-155 and miR-133b expression [39]. Secondly, environmental factors: different studies suggest that exposure to air pollution and passive tobacco smoking are independent risk factors for the development of both asthma [40,41] and obesity in children [42,43].…”

“…Excess fat mass in the chest wall and abdomen reduces the functional residual capacity of the lung (FRC) [37]. It is also associated with both reduced forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) [37][38][39][40][41][42][43][44][45]. Low tidal volume breaths due to thoracic and abdominal fat excess lead to low lung volumes [46], causing alveolar hypoventilation and an increase in airway resistance [47].…”

Airway immune response in the mouse models of obesity-related asthma

“…HFD was administered before mating and kept throughout pregnancy and lactation in a model of pediatric obese asthma. Then, offspring were sensitized to OVA at 6 weeks of age ( E-Lacerda et al, 2019 ). The results showed that the progeny of the obese mice displayed exacerbated responses and intense lung remodeling in the OVA-induced asthma model, which are featured by elevated IL-4, IL-13, TNF-α, TGF-β levels, leukocyte infiltration and collagen deposition.…”