Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da prole

• Ano de defesa: 2021
• Autor(a) principal: Parrela, Jocemara Patricia Silva de Souza
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Mato Grosso; Brasil; Instituto de Ciências da Saúde (ICS) - Sinop; UFMT CUS - Sinop; Programa de Pós-Graduação em Ciências em Saúde
• Palavras-chave em Português: Programação cardiometabólica; Desnutrição intrauterina; Leptina; Grelina; Obesidade; CNPQ::CIENCIAS DA SAUDE::MEDICINA; Cardiometabolic programming; Intrauterine malnutrition; Leptin; Ghrelin; Obesity
• Link de acesso: http://ri.ufmt.br/handle/1/5771

Intrauterine malnutrition at critical stages of development increases the vulnerability to metabolic diseases in adult life. The present study aimed to evaluate the effects of calorie restriction in the last third of gestation, on biometric, biochemical, molecular and functional parameters of just weaned and adult rat offspring, as well as on biochemical parameters of breast milk. Female Wistar rats were submitted to food restriction (50%) during the last third of gestation (FR50 group), while control rats were fed ad libitum throughout pregnancy (CONT group). At birth, the birthweight, number of livebirths, naso-anus length and sex of pups were assessed, as well as the litter size adjusted to 8 pups/mother. On the 6th, 11th and 16th day of lactation, milk intake was quantified. On the 12th day of lactation, a milk sample was taken to evaluate the energy content, biochemical parameters. On the 22nd day of age, weaning was performed, where a half of rat offspring was euthanized for tissue removal (white and brown adipose tissue and hypothalamus) for biometric and molecular analysis, and blood collected for biochemical analysis (glycemia, lipid and metabolic hormonal profile). In addition, mothers were euthanized for blood collection and subsequent biochemical analysis. The other half of rat offspring was kept into adulthood. Body weight and food intake were measured every two days. At 90 days of age, individual food intake in the dark cycle was evaluated. At 100 days of age, rat offspring were euthanized to collect blood, fat stores and skeletal muscle for biochemical and biometric analysis, and thoracic aorta removed and isolated to assess vascular reactivity. In relation to CONT mothers, milk from FR50 mothers display higher energy content (22%; P<0.05). It was richer in glucose (27%; P<0.01), total cholesterol (41%; P<0.05), triglycerides (2%; P<0.05), as well as with changes in the metabolic hormone values, rich in acylated ghrelin (70%; P<0.05) and poor in leptin (78%; P<0.001) and corticosterone (14%; P<0.05). Compared to CONT mothers, FR50 rats presented hypoglycemia (23%, P<0.001) and increased values of triglyceride (38%; P<0.01) and VLDL cholesterol (38%; P<0.01) and leptin (155%; P<0.001) without changes in acylated ghrelin and corticosterone levels. The FR50 rat offspring, compared to CONT rats, were born with small naso-anus length and body weight (P<0.001). During lactation, the evolution of body weight and milk intake in the FR50 group were higher compared to the CONT group (P<0.001). At weaning, FR50 rat offspring presented obese phenotype (P<0.001), hyperglycemia, insulin resistance and dyslipidemia (P<0.05), hyperghrelinemia (64%; P<0.05) and hyperleptinemia (82%; P<0.01), as well as up regulation of hypothalamic ghrelin receptor (~4-fold, P<0.01), when compared to CONT. Regarding data in adulthood, FR50 rats presented obese phenotype (P<0.05), hyperglycemia (12%; P<0.001), hypertriglyceridemia (16%; P<0.01), insulin resistance (+3%; P<0.001), dyslipidemia (P<0.05) and high Castelli I (+46%; P<0.01) and II (+59%; P<0.01) indices; as well as dysfunction in the vascular contractile response in the thoracic aorta (P<0.01). We conclude that malnutrition in the last third of gestation promotes changes in the biochemical, energetic and in the metabolic hormones composition in breast milk, possibly contributing to the programming of obese phenotype of rat offspring in childhood, which suggest a relation with hyperphagia and greater amount of ghrelin receptor in hypothalamus at this stage of development. In addition, it is summarized that the obese and dyslipidemic phenotype extend throughout life, and that FR50 rats are more likely to develop cardiovascular diseases.