Jin Junyan, Panserat Stéphane, Kamalam Biju Sam, Aguirre Peyo, Véron Vincent, Médale Françoise
INRA, UR 1067 Nutrition Metabolism Aquaculture, Institut National de la Recherche Agronomique, F-64310 Saint-Pée-sur-Nivelle, France.
INRA, UR 1067 Nutrition Metabolism Aquaculture, Institut National de la Recherche Agronomique, F-64310 Saint-Pée-sur-Nivelle, France.
Gen Comp Endocrinol. 2014 Aug 1;204:49-59. doi: 10.1016/j.ygcen.2014.04.027. Epub 2014 May 14.
Two experimental rainbow trout lines were developed through divergent selection for low (Lean 'L' line) or high (Fat 'F' line) muscle fat content. Previous nutritional studies suggested that these lines differed in their regulation of lipid and glucose metabolism. Since insulin acts as an anabolic hormone by regulating lipid and glucose metabolism, we put forward the hypothesis that F line might have a stronger sensitivity to insulin than L line. In order to test this hypothesis, bovine insulin was injected into rainbow trout of the two lines fasted for 48 h. As expected, insulin induced hypoglycemia and activated Akt-TOR signaling both in the liver and muscle of the two lines. We demonstrate that this was coupled with increased expression of insulin dependent glucose transporter (GLUT4) and transcription factors of fatty acid anabolism (LXR and SREBP1c) in the muscle and liver, respectively, and lower mRNA levels of fatty acid oxidation enzymes (CPT1a, CPT1b and HOAD) in the white muscle of both lines. Regarding the genotype effect, TOR signaling response to insulin was stronger in F line as reflected by the higher phosphorylation of S6 protein and elevated mRNA levels of lipogenic enzyme (FAS) in the liver of F line. This observation was concordant with the higher plasma concentrations of free fatty acids and triglycerides in F line. Moreover, mRNA levels of hepatic gluconeogenic enzymes (G6Pase2, FBPase and PEPCK) and muscle fatty acid oxidation enzymes (CPT1a, CPT1b, HOAD and ACO) were higher in the F line. However, very few insulin-genotype interactions were detected, indicating that insulin induced similar changes in lipid and glucose metabolism in both lines.
通过对低肌肉脂肪含量(瘦型“L”系)或高肌肉脂肪含量(肥型“F”系)进行差异选择,培育出了两个实验性虹鳟鱼品系。先前的营养研究表明,这些品系在脂质和葡萄糖代谢调节方面存在差异。由于胰岛素通过调节脂质和葡萄糖代谢发挥合成代谢激素的作用,我们提出假设,F系对胰岛素的敏感性可能比L系更强。为了验证这一假设,将牛胰岛素注射到禁食48小时的两个品系的虹鳟鱼体内。不出所料,胰岛素在两个品系的肝脏和肌肉中均诱导了低血糖并激活了Akt-TOR信号通路。我们证明,这与肌肉和肝脏中胰岛素依赖性葡萄糖转运蛋白(GLUT4)以及脂肪酸合成代谢转录因子(LXR和SREBP1c)的表达增加相关,并且两个品系的白色肌肉中脂肪酸氧化酶(CPT1a、CPT1b和HOAD)的mRNA水平降低。关于基因型效应,F系中TOR信号对胰岛素的反应更强,这体现在F系肝脏中S6蛋白的磷酸化水平更高以及脂肪生成酶(FAS)的mRNA水平升高。这一观察结果与F系中游离脂肪酸和甘油三酯的血浆浓度较高一致。此外,F系中肝脏糖异生酶(G6Pase2、FBPase和PEPCK)以及肌肉脂肪酸氧化酶(CPT1a、CPT1b、HOAD和ACO)的mRNA水平更高。然而,检测到的胰岛素-基因型相互作用很少,表明胰岛素在两个品系中诱导的脂质和葡萄糖代谢变化相似。