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AMPK和AKT/GSK3β信号通路参与重组蛋白成纤维细胞生长因子1(rFGF1和rFGF1a)改善高脂饮食虹鳟鱼的糖脂代谢。

The AMPK and AKT/GSK3β pathways are involved in recombinant proteins fibroblast growth factor 1 (rFGF1 and rFGF1a) improving glycolipid metabolism in rainbow trout () fed a high carbohydrate diet.

作者信息

Yu Huixia, Geng Shuo, Li Shuai, Wang Yingwei, Ren Xin, Zhong Debin, Mo Haolin, Yao Mingxing, Yu Jiajia, Li Yang, Wang Lixin

机构信息

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.

Meixian Aquaculture Farm of Shitouhe Reservoir Administration, Xianyang, Shaanxi, 712000, China.

出版信息

Anim Nutr. 2024 Jan 3;17:11-24. doi: 10.1016/j.aninu.2023.10.009. eCollection 2024 Jun.

Abstract

Fibroblast growth factor 1 (FGF1) regulates vertebrate cell growth, proliferation and differentiation, and energy metabolism. In this study, we cloned rainbow trout () and , prepared their recombinant proteins (rFGF1 and rFGF1a), and described the molecular mechanisms by which they improve glycolipid metabolism in carnivorous fish. A 31-d feeding trial was conducted to investigate whether they could enhance glycolipid metabolism in rainbow trout on high-carbohydrate diets (HCD). A total of 720 rainbow trout (8.9 ± 0.5 g) were equally divided into 4 groups: the chow diet (CD) group injected with PBS, the HCD group injected with PBS, the HCD group injected with rFGF1 (400 ng/g body weight), and the HCD group injected with rFGF1a (400 ng/g body weight). The results showed that short-term HCD had a significant positive effect on the specific growth rate (SGR) of rainbow trout ( < 0.05). However, it led to an increase in crude fat, serum triglyceride (TG) and glucose content, as well as serum glutamic pyruvic transaminase (GPT) and glutamic oxalacetic transaminase (GOT) contents ( 0.05), suggesting a negative health effect of HCD. Nevertheless, rFGF1 and rFGF1a showed beneficial therapeutic effects. They significantly reduced the crude fat content of the liver, serum TG, GOT, and GPT contents caused by HCD ( < 0.05). The upregulation in , , and mRNAs implied the promotion of TG catabolism. Moreover, rFGF1 and rFGF1a contributed to promoting lipolysis by activating the AMPK pathway and reducing lipid accumulation in the liver caused by HCD. In addition, the rFGF1 and rFGF1a-treated groups significantly reduced serum glucose levels and elevated hepatic glycogen content under HCD, and increased glucose uptake by hepatocytes. We observed a decrease in mRNA levels for , , and , along with an increase in mRNA levels for , , and in the liver. Furthermore, these proteins regulated hepatic gluconeogenesis and glycogen synthesis by increasing the phosphorylation level of AKT, ultimately leading to an increase in GSK3β phosphorylation. In conclusion, this study demonstrates that rFGF1 and rFGF1a can enhance lipolysis and glucose utilization in rainbow trout by activating the AMPK pathway and AKT/GSK3β axis.

摘要

成纤维细胞生长因子1(FGF1)调节脊椎动物细胞的生长、增殖和分化以及能量代谢。在本研究中,我们克隆了虹鳟鱼的 和 ,制备了它们的重组蛋白(rFGF1和rFGF1a),并阐述了它们改善肉食性鱼类糖脂代谢的分子机制。进行了一项为期31天的饲养试验,以研究它们是否能增强高碳水化合物日粮(HCD)喂养的虹鳟鱼的糖脂代谢。总共720尾虹鳟鱼(8.9 ± 0.5 g)被平均分为4组:注射PBS的普通日粮(CD)组、注射PBS的HCD组、注射rFGF1(400 ng/g体重)的HCD组和注射rFGF1a(400 ng/g体重)的HCD组。结果表明,短期HCD对虹鳟鱼的特定生长率(SGR)有显著的正向影响( < 0.05)。然而,它导致粗脂肪、血清甘油三酯(TG)和葡萄糖含量增加,以及血清谷丙转氨酶(GPT)和谷草转氨酶(GOT)含量增加( 0.05),表明HCD对健康有负面影响。尽管如此,rFGF1和rFGF1a显示出有益的治疗效果。它们显著降低了HCD引起的肝脏粗脂肪含量、血清TG、GOT和GPT含量( < 0.05)。 、 和 mRNA的上调意味着TG分解代谢的促进。此外,rFGF1和rFGF1a通过激活AMPK途径和减少HCD引起的肝脏脂质积累,有助于促进脂肪分解。此外,rFGF1和rFGF1a处理组在HCD条件下显著降低了血清葡萄糖水平,提高了肝糖原含量,并增加了肝细胞对葡萄糖的摄取。我们观察到肝脏中 、 和 的mRNA水平下降,同时 、 和 的mRNA水平上升。此外,这些蛋白通过增加AKT的磷酸化水平来调节肝脏糖异生和糖原合成,最终导致GSK3β磷酸化增加。总之,本研究表明,rFGF1和rFGF1a可通过激活AMPK途径和AKT/GSK3β轴增强虹鳟鱼的脂肪分解和葡萄糖利用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c648/10912841/d02f94b1fded/gr1.jpg

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