de Vasconcelos Diogo Antonio Alves, Nachbar Renato Tadeu, Pinheiro Carlos Hermano, do Amaral Cátia Lira, Crisma Amanda Rabello, Vitzel Kaio Fernando, Abreu Phablo, Alonso-Vale Maria Isabel, Lopes Andressa Bolsoni, Bento-Santos Adriano, Falcão-Tebas Filippe, de Santana David Filipe, do Nascimento Elizabeth, Curi Rui, Pithon-Curi Tania Cristina, Hirabara Sandro Massao, Leandro Carol Góis
Department of Nutrition, Center of Health Sciences, Federal University of Pernambuco, Recife, Brazil.
Post-graduate Program in Nutrition, Physical Activity and Phenotypic Plasticity, Federal University of Vitória de Santo Antão, Vitória de Santo Antão, Brazil.
Front Nutr. 2022 Aug 30;9:947458. doi: 10.3389/fnut.2022.947458. eCollection 2022.
Several studies have demonstrated that a maternal low-protein diet induces long-term metabolic disorders, but the involved mechanisms are unclear. This study investigated the molecular effects of a low-protein diet during pregnancy and lactation on glucose and protein metabolism in soleus muscle isolated from adult male rats. Female rats were fed either a normal protein diet or low-protein diet during gestation and lactation. After weaning, all pups were fed a normal protein diet until the 210th day postpartum. In the 7th month of life, mass, contractile function, protein and glucose metabolism, and the Akt-mTOR pathway were measured in the soleus muscles of male pups. Dry weight and contractile function of soleus muscle in the low-protein diet group rats were found to be lower compared to the control group. Lipid synthesis was evaluated by measuring palmitate incorporation in white adipose tissue. Palmitate incorporation was higher in the white adipose tissue of the low-protein diet group. When incubated soleus muscles were stimulated with insulin, protein synthesis, total amino acid incorporation and free amino acid content, glucose incorporation and uptake, and glycogen synthesis were found to be reduced in low-protein diet group rats. Fasting glycemia was higher in the low-protein diet group. These metabolic changes were associated with a decrease in Akt and GSK-3β signaling responses to insulin and a reduction in RPS6 in the absence of the hormone. There was also notably lower expression of Akt in the isolated soleus muscle of low-protein diet group rats. This study is the first to demonstrate how maternal diet restriction can reduce skeletal muscle protein and mass by downregulating the Akt-mTOR pathway in adulthood.
多项研究表明，母体低蛋白饮食会诱发长期的代谢紊乱，但其相关机制尚不清楚。本研究调查了孕期和哺乳期低蛋白饮食对成年雄性大鼠比目鱼肌葡萄糖和蛋白质代谢的分子影响。雌性大鼠在妊娠和哺乳期分别喂食正常蛋白饮食或低蛋白饮食。断奶后，所有幼崽均喂食正常蛋白饮食直至产后第210天。在出生后第7个月，测量雄性幼崽比目鱼肌的质量、收缩功能、蛋白质和葡萄糖代谢以及Akt-mTOR通路。发现低蛋白饮食组大鼠比目鱼肌的干重和收缩功能低于对照组。通过测量棕榈酸酯在白色脂肪组织中的掺入来评估脂质合成。低蛋白饮食组白色脂肪组织中棕榈酸酯的掺入较高。当用胰岛素刺激孵育的比目鱼肌时，发现低蛋白饮食组大鼠的蛋白质合成、总氨基酸掺入和游离氨基酸含量、葡萄糖掺入和摄取以及糖原合成均减少。低蛋白饮食组的空腹血糖较高。这些代谢变化与胰岛素刺激下Akt和GSK-3β信号反应的降低以及无激素时RPS6的减少有关。低蛋白饮食组大鼠分离的比目鱼肌中Akt的表达也明显较低。本研究首次证明母体饮食限制如何通过在成年期下调Akt-mTOR通路来减少骨骼肌蛋白质和质量。
