Navegando por Palavras-chave "Metabolic Programming"

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    Estudo da expressão de proteínas SNARE no pâncreas endócrino de animais da prole de fêmeas de camundongo alimentadas com dieta hiperlipídica durante a gestação e lactação
    (Universidade Federal de São Paulo (UNIFESP), 2019-08-22) Oliveira, Daniele Correia de Sales Marques de [UNIFESP]; Carvalho, Carolina Prado de França [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The “metabolic programming” is a term which explains that, during the ontogenesis, the development of each organ or system have a critical sensibility window to environmental factors which can adjust the phenotype along life. Animal studies show that offsprings of diabetic females or dams fed a high-fat (HF) or low protein diets during pregnancy and lactation can present glucose homeostasis perturbations and increased risk to obesity and type 2 diabetes (T2D) development at long-term. In this way, the aim of this work was to study the later repercussion of the metabolic programming with HF diet (34% lipids in g) during pregnancy and lactation for the secretory function of pancreatic β-cell and the islet VAMP-2 expression, a v-SNARE protein. For this, were used C57BL/6J male adult mice, from the offspring of females fed a control diet (CON group) or a high-fat diet (HF group) during pregnancy and lactation. After weaning, animals from both groups were fed a control diet (4,5% lipids in g) until euthanasia (approximately 12 weeks of life). This study was approved by the Committee of Ethics in Animal Experimentation (CEUA – UNIFESP Nº: 1306150817). VAMP-2 is a SNARE protein that has a crucial role for exocytosis of insulin granules. Our results showed that animals from the HF-fed group at weaning had increased body weight (p<0.0001) and increased postprandial glycemia (p<0.0001), in relation to control group. However, in adult age (12 weeks) the body weight of mice from HF diet-fed group was decreased (p<0.004), in relation to control group, but the postprandial glycemia was not different between groups. Furthermore, mice from HF diet-fed group are also insulin resistant, as demonstrated by the ipITT AUC, expressed as percentage of the initial glycemia value (p<0.004), are hyperinsulinemic (p=0.02), and have increased insulin secretion increment in relation to the baseline condition (p<0.02). Hence, islets from mice of HF-diet fed group showed increased F-actin labelling (p<0.0001) and reduced immunostaining (p<0.0001) and protein levels of VAMP-2 (p<0.025). In conclusion, the metabolic programming with HF diet during pregnancy and lactation induces insulin resistance and a decrease in VAMP-2 expression in male mice islet from offsprings of HF diet-fed females analysed at adult age. These alterations may predispose these mice to late glucose homeostasis perturbations, which can culminate with type 2 diabetes development.
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    Estudo de alterações morfológicas e funcionais do pâncreas endócrino da prole de fêmeas de camundongo alimentadas com dieta hiperlipídica durante a gestação e lactação
    (Universidade Federal de São Paulo (UNIFESP), 2017-04-13) Fontes, Camila Calvo de [UNIFESP]; Carvalho, Carolina Prado de França [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Environmental conditions that we are exposed on the beginning of life can affect the functioning of several organs and systems, and consequently, the health in adult life. The “metabolic programming” term explain that, during the ontogenesis, the development of each organ or system have a critical sensibility window to environmental factors which can adjust the phenotype along of life. In case of the endocrine pancreas, some critical processes, such as: islet vascularization, determination of morphological features and the start of functional maturation of pancreatic β cell occur during the intrauterine life. The aim of this work was investigated changes in morphological and morphometrical aspects of endocrine pancreas and the functioning of pancreatic β cells of C57BL6 offspring from female mice fed a high fat (HFD, 34% fat) or control (CON, 4.5% fat) diets during pregnancy and lactation in different ages (at 3 and 12 days of post-natal life and in adulthood). 3-days aged animals from HFD-fed group showed decreased islet number per pancreas section (p=0.0084). For the 12-days group we observed hypertrophy (p=0.0006) and decreased number of β cells (p=0.0053) in HFD-fed animals. At weaning (on 21st day), the animals from HFD-fed group showed a significant increase in body weight (p=0.0058) and postprandial blood glucose (p=0.0002). However, for 12-week-old animals (at adult age) these differences disappeared. Nevertheless, the adult HFD-fed group showed increased weight of all fat depots studied, such as gonadal (p=0.0002), retroperitoneal (p=0.02) and mesenteric (p=0.0071). These animals still showed an impairment of glycemic homeostasis, characterized by glucose intolerance (AUC GTT p=0.03), insulin resistance (AUC ITT p=0.0005), hyperinsulinemia (p=0.0004), as well as a decrease of glucose removal rate (kITT; p=0.04). The morphometric analysis showed a significant increase in islet area, an increase in β-cell (p<0.0001 for both) and α-cells (p=0.0004) areas, besides an hypertrophy of β-cells (p<0.0001) of islets from mice of HFD-fed offspring, in comparison with mice from CON-fed offspring. In conclusion, the metabolic programming with HFD-diet during pregnancy and lactation caused adjustments in endocrine pancreas development of mice offspring, predisposing them to develop metabolic diseases, such as type 2-diabetes mellitus at adult age.