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Alpha-linolenic acid and linoleic acid differentially regulate the skeletal muscle secretome of obese Zucker rats

机译:α-亚麻酸和亚油酸差异调节肥胖Zucker大鼠的骨骼肌秘密

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Evidence shows that proteins secreted from skeletal muscle influence a broad range of metabolic signaling pathways. We previously reported that essential polyunsaturated fatty acids (PUFA) improved whole-body glucose homeostasis in obese Zucker rats; however, the mechanisms underlying these benefits remain enigmatic. While PUFA and obesity influence skeletal muscle function, their effects on the secretome are unknown. The aim of this work was to determine if improvements in whole-body glucose homeostasis in obese Zucker rats fed diets supplemented with either linoleic acid (LA) or alpha-linolenic acid (ALA) for 12 wk are related to changes in the skeletal muscle secretome. Secreted proteins were identified with a predictive bioinformatic analysis of microarray gene expression from red tibialis anterior skeletal muscle. Approximately 130 genes were differentially expressed (false discovery rate = 0.05) in obese rats compared with lean controls. The expression of 15 genes encoding secreted proteins was differentially regulated in obese controls, obese LA-supplemented, and obese ALA-supplemented rats compared with lean controls. Five secreted proteins (Col3a1, Col15a1, Pdgfd, Lyz2, and Angptl4) were differentially regulated by LA and ALA. Most notably, ALA supplementation reduced Angptl4 gene expression compared with obese control and obese-LA supplemented rats and reduced circulating ANGPTL4 serum concentrations. ALA also influenced Angptl4 gene expression and ANGPTL4 secretion from differentiated rat L6 myotubes. Altogether, the present data indicate that obesity has a greater global impact on skeletal muscle gene expression than either essential PUFA; however, LA and ALA may exert their metabolic benefits in part by regulating the skeletal muscle secretome.
机译:证据表明,从骨骼肌分泌的蛋白质会影响广泛的代谢信号通路。我们以前报道,基本的多不饱和脂肪酸(PUFA)改善了肥胖Zucker大鼠的全身葡萄糖稳态;然而,这些益处的基本机制仍然是神秘的。虽然pufa和肥胖影响骨骼肌功能,但它们对秘密的影响是未知的。这项工作的目的是确定肥胖Zucker大鼠全身葡萄糖稳态的改进,喂养补充有亚油酸(La)或α-亚麻酸(ALA)的饮食与12周有关的骨骼肌猝灭的变化有关。用来自红色胫骨前骨骼肌的微阵列基因表达的预测生物信息分析鉴定了分泌的蛋白质。与瘦对照相比,大约130个基因在肥胖大鼠中差异表达(假发现率= 0.05)。编码分泌蛋白质的15个基因的表达在肥胖对照中差异调节,肥胖的La-Conseplyed和肥胖的Ala补充大鼠与瘦对照组进行了相比。通过La和Ala差异调节五种分泌的蛋白质(COL3A1,COL15A1,PDGFD,LYZ2和ANGPTL4)。最值得注意的是,与肥胖对照和肥胖 - LA补充大鼠相比,ALA补充减少了Angptl4基因表达,并降低了循环的Angptl4血清浓度。 ALA还影响了来自分化的大鼠L6 myotubes的Angptl4基因表达和Angptl4分泌。总之,目前的数据表明肥胖对骨骼肌基因表达具有更大的全局影响,而不是必需的PUFA;然而,La和Ala可以通过调节骨骼肌ecricsome来施加它们的代谢益处。

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