Impacto transgeracional do diabete materno sobre a morfofisiologia mitocondrial e expressão proteica do músculo esquelético de ratas fêmeas adultas
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Data
2021-10-20
Autores
Kloppel, Eduardo
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Universidade Estadual Paulista (Unesp)
Resumo
O diabetes materno tem um impacto negativo no fenótipo da prole, o que contribui para um metabolismo prejudicado na idade adulta. No entanto, os mecanismos sob esses resultados ainda não são claros. Neste estudo, utilizando um modelo de rato, objetivamos investigar o impacto do diabetes materno no metabolismo de filhotes de fêmeas adultas em relação à dinâmica mitocondrial e à ultraestrutura do músculo esquelético. Para tanto, filhotes fêmeas procedentes de mães diabéticas (FOD) foram obtidas através da gestação de ratas Sprague-Dawley com diabetes induzido por estreptozotocina neonatal. As mães controle receberam tampão de citrato durante sua vida neonatal. Na idade adulta, ratos FOD e Controle foram submetidos ao teste oral de tolerância à glicose (OGTT) para critérios de inclusão nos grupos. Aos 150 dias de vida, os ratos FOD e Controle foram sacrificados para coleta de amostras de sangue e músculo. Os ratos FOD apresentaram níveis mais elevados de insulina e triglicerídeos e OGTT anormal. Esses animais também apresentaram diminuição da ativação de marcadores moleculares de sinalização da insulina e função mitocondrial e ultraestrutura do músculo sóleo prejudicadas. Assim, o impacto transgeracional do diabetes materno causou plasticidade fetal, o que levou à resistência à insulina e intolerância à glicose na idade adulta, e a rede mitocondrial do músculo esquelético mostrou ter um papel importante durante o estado pré-diabético.
Maternal diabetes has a negative impact on offspring phenotype, which contributes to an impaired metabolism in adulthood. Nonetheless, the mechanisms under these outcomes are still unclear. In this study by utilizing a rat model, we aimed to investigate the impact of maternal diabetes on the metabolism of adult female offspring in relation to mitochondrial dynamics, and ultrastructure of skeletal muscle. For this, female offspring coming from diabetic mothers (FOD) were obtained through pregnancy of Sprague-Dawley rats with streptozotocin neonatally-induced diabetes. Control mothers received citrate buffer during their neonatal life. At adulthood, FOD and Control rats were submitted to oral glucose tolerance test (OGTT) for inclusion criteria in the groups. At 150 days of life, the FOD and Control rats were sacrificed for collection of blood and muscle samples. The FOD rats presented a higher insulin and triglyceride levels, and abnormal OGTT. These animals also showed decreased activation of molecular markers of insulin signaling, and impaired mitochondrial function and ultrastructure in soleus muscle. Thus, the transgenerational impact of maternal diabetes caused fetal plasticity, which led to insulin resistance and glucose intolerance at adulthood, and the mitochondrial network of skeletal muscle is shown to have an important role during the prediabetic state.
Maternal diabetes has a negative impact on offspring phenotype, which contributes to an impaired metabolism in adulthood. Nonetheless, the mechanisms under these outcomes are still unclear. In this study by utilizing a rat model, we aimed to investigate the impact of maternal diabetes on the metabolism of adult female offspring in relation to mitochondrial dynamics, and ultrastructure of skeletal muscle. For this, female offspring coming from diabetic mothers (FOD) were obtained through pregnancy of Sprague-Dawley rats with streptozotocin neonatally-induced diabetes. Control mothers received citrate buffer during their neonatal life. At adulthood, FOD and Control rats were submitted to oral glucose tolerance test (OGTT) for inclusion criteria in the groups. At 150 days of life, the FOD and Control rats were sacrificed for collection of blood and muscle samples. The FOD rats presented a higher insulin and triglyceride levels, and abnormal OGTT. These animals also showed decreased activation of molecular markers of insulin signaling, and impaired mitochondrial function and ultrastructure in soleus muscle. Thus, the transgenerational impact of maternal diabetes caused fetal plasticity, which led to insulin resistance and glucose intolerance at adulthood, and the mitochondrial network of skeletal muscle is shown to have an important role during the prediabetic state.
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Palavras-chave
Diabetes, Mitochondria, Skeletal muscle, DOHaD, Insulin resistance, Fetal programming