Obesidade parental e programação fetal: fígado e via de sinalização da leptina (JAK/STAT) no hipotálamo da prole

• Autor(a) principal: Cruz, Fernanda Ornellas Pinto da
• Data de Publicação: 2015
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/7789
• topic: Maternal obesity; Paternal obesity; Parental obesity; Liver; Hypothalamus; Obesidade materna; Obesidade paterna; Obesidade parental; Fígado; Hipotálamo; Obesidade; Obesidade nas mulheres; Obesidade nos homens; Fígado; Leptina; Hipotálamo; CNPQ::CIENCIAS BIOLOGICAS

Maternal obesity may reflect in deleterious effects on adult offspring, however, recent studies have indicated the father's participation in this outcome. This study aimed to evaluate the effects of maternal and/or paternal obesity upon male and female offspring in body mass, carbohydrates and lipids metabolism, the components of the lipogenesis and hepatic beta-oxidation, the mediators of leptin signaling pathway (JAK/STAT) and appetite regulatory neurotransmitter, as well as the local inflammatory markers. C57BL/6 males and females with four weeks of age were divided into two groups: control diet (SC, 17% of energy from lipids) or high-fat diet (HF, 49% of energy from lipids). The mating occurred when the parents completed 12 weeks of age, and at birth, the offspring were identified according to the maternal and paternal diets and sex. The offspring received SC diet of the weaning to 12 weeks of age, when they were sacrificed. We evaluated the body mass (BM), food intake, insulin and plasma leptin, lipid profile, glucose tolerance, hepatic triglyceride (TG) and estimate of hepatic steatosis, with analysis of gene and protein expression of components of the beta-oxidation and lipogenesis, leptin signaling pathway (JAK/ STAT) in the hypothalamus, local inflammation and presence of gene and protein expression of appetite regulating neurotransmitters. Differences between groups were analyzed by One Way ANOVA followed by post- test of Holm-Sidak as interactions between maternal and paternal diet and sex of offspring were evaluated using the Three Way ANOVA. In all cases, P<0.05 was considered statistically significant. Offspring of obese mothers: elevation in BM from the second week of life (p<0.01), hyperleptinemia, hyperinsulinemia and glucose intolerance with worsening in lipid profile at the end of the experiment (p<0.001). These groups showed hepatic steatosis, with activation of lipogenesis and inhibition of beta-oxidation, resulting in elevation of hepatic TG. There was decrease in OBRb receptor with impairment of JAK/STAT pathway, increase in SOCS3, elevation in gene and protein expression of NPY, decreased POMC, resulting in hyperphagia (p<0.0001) and hypothalamic inflammation (p<0.001). Offspring of obese fathers: the offspring showed glucose intolerance and hyperinsulinemia (p<0.01), hepatic steatosis by the activation of lipogenesis, with no change in the JAK/STAT and feeding behavior, but with initial presence of local inflammation. Offspring of obese parents: were heavier at birth (p <0.01) and all the deleterious effects observed were maximized. Maternal obesity results in obesity, metabolic and hepatic disorders and in hyperphagia, due to changes in leptin signaling in the hypothalamus, associated with local inflammation. The paternal obesity causes glucose intolerance, hyperinsulinemia, hepatic steatosis and presence of initial hypothalamic inflammation, however, when both parents are obese, these effects are maximized in the offspring.