Maternal obesity in mice programs the intensification of allergic response inflammation in the offspring

Author(s)

Rodrigo Rodrigues e Lacerda

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2019-07-31

Examining board members

Gabriel Forato Anhê; Marco Aurélio Ramirez Vinolo; Marcelo Nicolas Muscara; Soraia Katia Pereira Costa; Wothan Tavares de Lima

• Advisor: Gabriel Forato Anhê

Abstract

Maternal obesity during gestation and lactation is a condition that can lead to numerous diseases in the postnatal life of the offspring in the short and long term. Metabolic, immunological and structural pathways are negatively modified in the new life in formation under the action of excess fat on the parent, including respiratory diseases, such as asthma, which may be precipitated in childhood and adulthood. The aim of this study was to evaluate, using murine models of obesity and experimental asthma, whether the presence of obesity by the mother during gestation/lactation may result in an aggravation of the allergic inflammatory response of the male offspring in adult life. C57B1/6 mice were submitted to fattening by an intermittent hyperlipidic diet for 6 weeks and during crossing, gestation and lactation. The offspring of male animals were evaluated for inflammatory criteria in adult life comparing with offspring of mothers who ate normolipidic diet for the same period. Maternal obesity induced in the offspring the increase of the leukocyte migration to the bronchoalveolar lavage, stimulating the increase in the number of eosinophils and neutrophils. The same result was observed in the lung tissue, which in addition to tissue leucocytosis, showed a high destruction of the epithelial layer, hypertrophy and smooth muscle hyperplasia and thickening of the subepithelial layer. Levels of IgE, IL-4 and IL-13 also remained elevated in this group. No differences were observed in IL-5 and IL-10 levels. The obese children presented a high pulmonary remodelling with increased levels of collagen and TGB-?1, as well as exacerbation of mucus production and number of goblet cells. Elevation of phosphorylated TNF-? and NF-?B levels and reduction of A20 protein expression may indicate a possible activation of the inflammasome pathway. No significant differences in IL-1? levels were noted. The expression of miRNA-133b has been shown to be decreased in the trachea and lung tissue of obese offspring, and the miRNA-155 which has been shown to be elevated in peripheral lymphocytes of the same group. The data set reveals that maternal obesity can severely compromise their offspring, acting on migration and cellular activation, on the expression of inflammatory proteins, and negatively regulating gene expression (AU)

• FAPESP's process: 15/18997-7 - Evaluation of the allergic response in the offspring born to and breastfed by obese and lean mice exposed to ovalbumin.
• Grantee: Rodrigo Rodrigues e Lacerda
• Support Opportunities: Scholarships in Brazil - Doctorate