Maternal protein restriction during early lactation induces GLUT4 translocation and mTOR/Akt activation in adipocytes of adult rats
Maternal protein restriction during early lactation induces GLUT4 translocation and mTOR/Akt activation in adipocytes of adult rats
复制标题
DOI：
10.1152/ajpendo.00439.2007
复制
发表时间：
2008-09-01
影响因子：
5.1
通讯作者：
Barja-Fidalgo, Christina
中科院分区：
文献类型：
--
作者：
Garcia-Souza, Erica Patricia;da Silva, Simone Vargas;Barja-Fidalgo, Christina
流行病学和实验研究表明，出生后早期营养与成年期葡萄糖稳态的长期影响有关。最近，我们的小组证明，在哺乳早期营养不良影响的表达和激活的关键蛋白的胰岛素信号级联在大鼠骨骼肌在出生后的发展。为了阐明生命早期营养不良导致外周组织胰岛素敏感性变化的分子机制，我们研究了脂肪组织中的胰岛素信号。从成年雄性大鼠的附睾脂肪垫中分离脂肪细胞，所述大鼠是在哺乳期的前10天期间饲喂正常或无蛋白质饮食的母鼠的后代。在进行免疫印迹分析、2-脱氧葡萄糖摄取、GLUT 4和/或肌动蛋白丝的免疫细胞化学分析之前，将细胞与100 nM胰岛素孵育。胰岛素刺激后，与对照组相比，从营养不良大鼠中分离的脂肪细胞IR和IRS-1的酪氨酸磷酸化降低，IRS-2、Akt和mTOR的基础磷酸化增加。基础葡萄糖摄取增加的脂肪细胞从营养不良组，和治疗LY 294002诱导只有部分抑制基础和胰岛素刺激的葡萄糖摄取，这表明参与磷酸肌醇3-激酶活性。这些变化伴随着更高的GLUT 4含量在质膜和肌动蛋白细胞骨架动力学的改变。这些数据表明，出生后早期营养不良损害胰岛素敏感性在成年期促进脂肪组织中的胰岛素信号的关键步骤的变化，这可能有助于葡萄糖稳态的永久性变化。
Epidemiological and experimental studies have demonstrated that early postnatal nutrition has been associated with long-term effects on glucose homeostasis in adulthood. Recently, our group demonstrated that undernutrition during early lactation affects the expression and activation of key proteins of the insulin signaling cascade in rat skeletal muscle during postnatal development. To elucidate the molecular mechanisms by which undernutrition during early life leads to changes in insulin sensitivity in peripheral tissues, we investigated the insulin signaling in adipose tissue. Adipocytes were isolated from epididymal fat pads of adult male rats that were the offspring of dams fed either a normal or a protein-free diet during the first 10 days of lactation. The cells were incubated with 100 nM insulin before the assays for immunoblotting analysis, 2-deoxyglucose uptake, immunocytochemistry for GLUT4, and/or actin filaments. Following insulin stimulation, adipocytes isolated from undernourished rats presented reduced tyrosine phosphorylation of IR and IRS-1 and increased basal phosphorylation of IRS-2, Akt, and mTOR compared with controls. Basal glucose uptake was increased in adipocytes from the undernourished group, and the treatment with LY294002 induced only a partial inhibition both in basal and in insulin-stimulated glucose uptake, suggesting an involvement of phosphoinositide 3-kinase activity. These alterations were accompanied by higher GLUT4 content in the plasma membrane and alterations in the actin cytoskeleton dynamics. These data suggest that early postnatal undernutrition impairs insulin sensitivity in adulthood by promoting changes in critical steps of insulin signaling in adipose tissue, which may contribute to permanent changes in glucose homeostasis.