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An immunological approach to the relationship between maternal and fetal adiposity in fetal, neonatal and infant periods

Grant number: 17/07143-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2017
Effective date (End): December 31, 2018
Field of knowledge:Health Sciences - Nutrition - Nutritional Analysis of Population
Principal researcher:Patricia Helen de Carvalho Rondó
Grantee:Naiara Naiana Dejani
Home Institution: Faculdade de Saúde Pública (FSP). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:15/03333-6 - The relationship between maternal adiposity and adiposity of the offspring in the fetal, neonatal and infant periods: a prospective population-based study, AP.TEM

Abstract

The prevalence of overweight and obesity is rising worldwide, and in pregnant women it may represent a short and long-term risk for the mother-baby binomial. Chronic non-communicable diseases such as hypertension, type 2 diabetes, dyslipidemia and cardiovascular diseases are more frequent in the presence of overweight and obesity due to the complex relationship between nutrition and inflammatory response. The purpose of the present study is to evaluate in lean and obese women and their offspring: a) inflammatory/immunological blood markers in the first and third trimesters of pregnancy and in the umbilical cord; b) inflammatory and stress markers in immune cells (macrophages) of pregnant women in the third trimester of pregnancy and umbilical cord, stimulated ex vivo with obesogenic stimulus. The presence of maternal obesity is expected to be related to blood inflammatory parameters, which may alter the expression of target genes and signaling pathways in circulating cells of the immune system. The innovative ex vivo approach will be relevant to explore the relationship between the body macroenvironment and the cellular microenvironment, challenged with nutritional stimuli, which would be difficult to observe in vivo. In addition to the anthropometric and body composition data, plasma cytokines TNF, IL-1², IL-6, IL-8, IL-10, MCP-1, MIP-1 will be determined. The ex vivo approach will be performed using macrophages isolated from blood and exposed to high glucose, high free fatty acids and lipopolysaccharide (LPS). Some nutritional sensors such as NAD-dependent protein deacetylase sirtuin-1 (SIRT1), AMP-activated protein kinase (AMPK), and the inflammatory cascade heat shock protein-70 (HSP70), toll-like receptors (TLRs) and cyclooxygenase-2 (COX-2) will be investigated. According to our knowledge, there is no cohort study and ex vivo approach that evaluates the adiposity of pregnant women and their offspring. The data obtained will be analyzed by biological models to explain the causal path of the relationship between maternal adiposity and infant weight gain. Such models that evaluate the relationship between the response variables and immunological parameters will be determined by regression multivariate models, comparing the results obtained in the groups of obese and lean pregnant women, with the umbilical cord results. In the final models p <0.05 will be considered significant.

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