The effects of maternal obesity during gestation and lactation and orange juice intake on the metabolic profile of male offspring exposed to control and obesogenic diets and breast cancer risk of female offspring

• Ano de defesa: 2020
• Autor(a) principal: Castro, Natália Pinheiro de
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Breast cancer; Câncer de mama; Early life; Início da vida; Obesidade; Obesity; Orange juice; Suco de laranja
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/9/9132/tde-03122020-200908/

Obesity is a worldwide public health problem and the main risk factor for a number of chronic diseases. Breast cancer is another worrisome disease: it is the leading cause of cancer amongst women and has an elevated mortality rate. Approximately 30 years ago, Barker and Trichopoulos suggested that cardiovascular disease and breast cancer, respectively, may be originated in utero. In subsequent years, studies proved both hypotheses correct. Understanding how in-utero environment can affect development of obesity and breast cancer in adulthood is key for preventing these diseases. Nutrition during gestation and lactation is considered a modifiable factor to impact in-utero environment. Orange juice (OJ) is an excellent source of bioactive compounds, including vitamin C and flavonoids, and reports suggests that intake of orange juice minimizes damaging effects of obesity. The objective of this thesis was to evaluate the effects of maternal obesity during gestation and lactation and OJ intake on (a) metabolic profile of male offspring exposed to control and obesogenic diets and (b) breast cancer risk of female offspring. Four-week-old C57BL/6 female mice were assigned into three groups: control- fed a control diet and water ad libitum, obese- fed obesogenic diet and water ad libitum and obese+OJ- fed obesogenic diet and OJ. After three weeks on the diet, females were mated to control males. Male offspring from each group were weaned into control or obesogenic diets for 21 weeks. Female offspring was either euthanized for evaluation of mammary gland development or submitted to a chemically induced breast carcinogenesis protocol. Parameters to assess metabolism (as body composition and adipose tissue expression of obesity-related genes), breast cancer risk (as epithelial elongation and number of terminal end buds) and tumorigenesis (incidence, latency and multiplicity of mammary tumors) were collected. ANOVA followed by Tukey or Fischer´s LSD test were used to investigate differences between groups and a p<0.05 was considered significant. Male offspring of obese mothers fed control diet presented increased glucose concentrations and expression of F4/80 and interleukin-6 compared to control offspring. Male offspring of obese+OJ mothers fed a control diet presented expression of F4/80 and interleukin-6 similar to control offspring. Male offspring to control mothers fed obesogenic diet presented increased glucose concentrations and epidydimal fat tissue compared to offspring of obese mothers. Offspring to obese+OJ mothers presented increased expression of leptin and tumor necrosis factor-&#945;. Female offspring of obese mothers had decreased terminal end buds and increased latency of first tumor and OJ intake decreased epithelial elongation compared to offspring of control/obese mothers. Maternal obesity had greater impact in offspring exposed to control than obesogenic environment. OJ intake by mothers helped with harmful effects induced by maternal obesity on male offspring fed control diet. Control offspring exposed to obesogenic diet presented worse metabolic profile than offspring from obese mothers. In this particular case, OJ was not beneficial to male offspring. Whereas obesity induced by a high-fat high-sugar diet presented a somewhat protective effect on breast cancer risk, OJ further protected offspring of obese mothers.