Transitory history of obesity during different moments of life and its impact on allergy airway disease

Abstract

Obesity is a highly prevalent condition that associates the positive energy balance with a chronic subclinical inflammatory state characterized by elevated levels of TNF± and IL-6 and increased infiltration of M1 macrophages in white adipose tissue. The exacerbation of the TH2 inflammatory response of allergic asthma is another characteristic observed in obese humans and mice. Some adaptations to obesity, such as hepatic steatosis and hyperleptinemia, have been described as persistent after weight loss. However, it is not known whether all inflammatory changes in obesity persist after weight loss. Thus, the aim of the present study is to determine whether the transient history of obesity at different times in life has a persistent effect on the exacerbation of the inflammatory response in an experimental model of allergic asthma in both genders. To achieve this goal, female and male C57BL/6 mice will be exposed to a transient history by HFD consumption (OB-Rev) or to permanent exposure to HFD (OB) or standard feed (CTL). The obesity episode in the OB-Rev groups will occur either during puberty or after puberty. These animals will be sensitized and challenged with chicken egg ovalbumin (OVA) to induce the allergic asthma model. As outcomes, we will analyze bronchoalveolar lavage (BAL) cells for the presence of eosinophils and neutrophils. BAL samples will be used to evaluate the levels of IL-4, IL-5, IL-10, IL-13, TGF-²1, TNF-± and IL-1². The serum will be used to assess IgE levels. The lung tissue will be evaluated for collagen deposition, leukocyte infiltration, mucus accumulation and expression of inflammatory pathway proteins. Lung function will be assessed in vivo with flexiVent equipment. The adipose tissue will be used to evaluate determinants of the obese phenotype (relative weight and expression of IL-6, leptin and adiponectin). (AU)