Department of Biological Sciences, Texas Tech University, Lubbock, Texas.
Department of Biological and Environmental Sciences, University of Gothenburg, Gothenburg, Sweden.
Am J Physiol Regul Integr Comp Physiol. 2022 May 1;322(5):R434-R444. doi: 10.1152/ajpregu.00254.2021. Epub 2022 Mar 16.
Catabolic conditions often induce concomitant changes in plasma leptin (Lep), growth hormone (GH), and insulin growth factor I (IGF-I) levels in teleost fish, but it is unclear whether these parts of the endocrine system are responding independently or functionally linked. In this study, fasted rainbow trout was used to study the effects of Lep on the GH-IGF-I system and metabolism. Fish were implanted intraperitoneally with recombinant rainbow trout Lep pellets and remained unfed. After 4 days, plasma GH levels were elevated in the Lep-treated fish in a dose-dependent manner; the expression of hepatic and plasma IGF-I levels were suppressed accordingly. In vitro Lep treatment reversed ovine GH (oGH)-stimulated expression of and in hepatocytes isolated from fasted fish, similar to the inhibitory effects of the MEK1/2 inhibitor U0126 treatment. However, Lep treatment alone had no effect on the expression of s or oGH-stimulated expression in the hepatocytes. These results demonstrate an additive effect of Lep on suppression of IGF-I under catabolic conditions, indicating that Lep is likely involved in initiation of acquired GH resistance. Although the Lep-implant treatment had no effect on standard metabolic rate, it significantly suppressed gene expression of hepatic hydroxyacyl-CoA dehydrogenase, phosphoenolpyruvate carboxykinase, and glucose 6-phosphatase, which are key enzymes in lipid utilization and gluconeogenesis, in different patterns. Overall, this study indicates that the Lep increase in fasting salmonids is an important regulatory component for physiological adaptation during periods of food deprivation, involved in suppressing growth and hepatic metabolism to spare energy expenditure.
在一些鱼类中，分解代谢的条件常常会引起瘦素（Lep）、生长激素（GH）和胰岛素样生长因子 I（IGF-I）的水平发生变化，但尚不清楚这些内分泌系统的组成部分是独立响应还是功能相关联的。在本研究中，使用饥饿的虹鳟来研究 Lep 对 GH-IGF-I 系统和代谢的影响。将重组虹鳟 Lep 微球通过腹膜内植入到鱼体中，使鱼保持不进食。4 天后，Lep 处理组鱼的血浆 GH 水平呈剂量依赖性升高；肝组织中 和血浆 IGF-I 水平的表达相应受到抑制。体外 Lep 处理逆转了分离自禁食鱼的肝细胞中 oGH 刺激的 和 的表达，与 MEK1/2 抑制剂 U0126 处理的抑制作用相似。然而，Lep 单独处理对 s 的表达或 oGH 刺激的 在肝细胞中的表达没有影响。这些结果表明，在分解代谢条件下，Lep 对 IGF-I 的抑制具有累加效应，表明 Lep 可能参与了获得性 GH 抵抗的发生。尽管 Lep 植入处理对标准代谢率没有影响，但它以不同的模式显著抑制了肝组织中羟酰基辅酶 A 脱氢酶、磷酸烯醇丙酮酸羧激酶和葡萄糖 6-磷酸酶的基因表达，这些酶是脂质利用和糖异生的关键酶。总体而言，本研究表明，禁食鲑鱼中 Lep 的增加是在饥饿期间生理适应的重要调节组成部分，涉及到抑制生长和肝代谢以节省能量消耗。
