Profiling growth performance, insulin-like growth factors (IGFs), and IGF-binding proteins (IGFBPs) in rainbow trout lacking IGFBP-2b.

Beth M Cleveland, Ayaka Izutsu, Yuika Ushizawa, Lisa Radler, Munetaka Shimizu
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Abstract

Insulin-like growth factor binding proteins (IGFBP) regulate insulin-like growth factor (IGF) signaling, but IGFBP-specific functions are not well characterized in fishes. A line of rainbow trout (Oncorhynchus mykiss) lacking a functional IGFBP-2b was produced using gene editing and subsequent breeding to an F2 generation. This loss-of-function model (2bKO) was subjected to either continuous feeding or feed deprivation (3 wk) followed by refeeding (1 wk). During continuous feeding, the 2bKO line displayed faster specific growth rate for both body weight and fork length, higher feed intake, and reduced feed conversion ratio compared to a wild type (WT) line. However, loss of IGFBP-2b did not affect the feed deprivation or refeeding response in terms of weight loss or weight gain, respectively. Several components of the IGF/IGFBP system were affected by loss of IGFBP2b. Total serum IGF-1 in the 2bKO line was reduced to 0.5 - 0.8-fold of the WT line although the concentration of free serum IGF-1 was not affected. Gene expression differences include reduced abundance of igfbp1a1, igfbp1b2, igfbp5b2, and igfbp6b1 transcripts, and elevated igf2 and igfbp6b2 transcripts in liver of the 2bKO line. Collectively, these findings suggest that although IGFBP-2b is a carrier of circulating IGF-1 in salmonids, the presence of IGFBP-2a and compensatory responses of other IGF/IGFBP system components support an anabolic response that improved growth performance in the loss-of-function model.

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分析缺乏 IGFBP-2b 的虹鳟的生长性能、胰岛素样生长因子(IGFs)和 IGF 结合蛋白(IGFBPs)。
胰岛素样生长因子结合蛋白(IGFBP)可调节胰岛素样生长因子(IGF)信号传导,但在鱼类中,IGFBP的特异性功能尚不十分明确。我们利用基因编辑技术培育出了缺乏功能性 IGFBP-2b 的虹鳟鱼(Oncorhynchus mykiss)品系,并随后培育出了 F2 代。对这种功能缺失模型(2bKO)进行持续喂养或饲料剥夺(3 周),然后再喂养(1 周)。与野生型(WT)品系相比,在连续饲喂期间,2bKO 品系的体重和叉长的特定生长速度更快,饲料摄入量更高,饲料转化率降低。然而,IGFBP-2b的缺失并不影响饲料剥夺或再喂养对体重减轻或体重增加的反应。IGF/IGFBP系统的几个组成部分受到IGFBP-2b缺失的影响。虽然游离血清 IGF-1 的浓度未受影响,但 2bKO 株系的血清总 IGF-1 降低到 WT 株系的 0.5 - 0.8 倍。基因表达差异包括 2bKO 株系肝脏中 igfbp1a1、igfbp1b2、igfbp5b2 和 igfbp6b1 转录本的丰度降低,igf2 和 igfbp6b2 转录本升高。总之,这些发现表明,虽然 IGFBP-2b 是鲑鱼体内循环 IGF-1 的载体,但 IGFBP-2a 的存在和其他 IGF/IGFBP 系统成分的代偿反应支持合成代谢反应,从而改善了功能缺失模型的生长性能。
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来源期刊
CiteScore
5.30
自引率
3.60%
发文量
145
审稿时长
2 months
期刊介绍: The American Journal of Physiology-Regulatory, Integrative and Comparative Physiology publishes original investigations that illuminate normal or abnormal regulation and integration of physiological mechanisms at all levels of biological organization, ranging from molecules to humans, including clinical investigations. Major areas of emphasis include regulation in genetically modified animals; model organisms; development and tissue plasticity; neurohumoral control of circulation and hypertension; local control of circulation; cardiac and renal integration; thirst and volume, electrolyte homeostasis; glucose homeostasis and energy balance; appetite and obesity; inflammation and cytokines; integrative physiology of pregnancy-parturition-lactation; and thermoregulation and adaptations to exercise and environmental stress.
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