Northwest A&F University, China.
Northwest A&F University, China.
Int J Biol Macromol. 2024 Nov;281(Pt 3):136226. doi: 10.1016/j.ijbiomac.2024.136226. Epub 2024 Oct 9.
High-fat diets (HFDs) are widely used in aquaculture due to their lipid and protein-conserving effects, thereby reducing feed costs. However, prolonged feeding of HFD often leads to metabolic disorders in fish, such as disruption of hepatic lipid homeostasis, liver injury, and disruption of glucose homeostasis. Fibroblast growth factor 1 (FGF1) plays an essential role in controlling glucose levels in the body and dampening immune reactions. However, its impact on teleosts remains poorly researched. The therapeutic potential of recombinant FGF1 (rFGF1) was examined in a 6-week culture experiment involving rainbow trout (Oncorhynchus mykiss) that were fed an HFD. The results revealed that rFGF1 significantly reduced serum glucose levels and hepatic PEPCK and G6PC activities, but improved hepatic glycogen (P < 0.05), compared to the HFD + PBS group. Further experiments indicated that the inhibitory effect of rFGF1 on hepatic gluconeogenesis was mediated by the cAMP signaling pathway and was dependent on the high expression of PDE4D. In addition, rFGF1 increased hepatic glycogen content, which involves the AKT-GSK3β axis. Despite this increase, rFGF1 did not lead to glycogen storage disease, as shown by reduced hepatic inflammation as a result of decreased GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), and elevated SOD (superoxide dismutase) in the rFGF1-treated group, accompanied by decreased il-1β, il-6, and xbp-1, and elevated nrf2 and number of hepatocyte autophagosomes. Alterations in gut microbes and short-chain fatty acids (SCFAs) were noted, indicating that rFGF1 caused a notable rise in intestinal Lactobacillus, acetic acid, and butyric acid levels. This study investigated the molecular mechanisms of rFGF1 on glucose metabolism and inflammatory responses in an HFD-fed rainbow trout model, providing new insights to improve the regulation of glucose metabolism in carnivorous fish.
高脂肪饮食（HFD）由于其具有保存脂质和蛋白质的作用，从而降低了饲料成本，因此在水产养殖中被广泛应用。然而，长期喂食 HFD 常导致鱼类发生代谢紊乱，如破坏肝内脂质稳态、肝损伤和破坏葡萄糖稳态。成纤维细胞生长因子 1（FGF1）在控制体内血糖水平和抑制免疫反应方面发挥着重要作用。然而，其在硬骨鱼类中的作用仍研究甚少。本研究在虹鳟（Oncorhynchus mykiss） 6 周养殖实验中，检测了重组 FGF1（rFGF1）的治疗潜力，虹鳟喂食高脂肪饮食。结果表明，与 HFD+PBS 组相比，rFGF1 显著降低了血清葡萄糖水平和肝 PEPCK 和 G6PC 活性，同时提高了肝糖原（P<0.05）。进一步的实验表明，rFGF1 对肝糖异生的抑制作用是通过 cAMP 信号通路介导的，并且依赖于 PDE4D 的高表达。此外，rFGF1 增加了肝糖原含量，涉及 AKT-GSK3β 轴。尽管肝糖原含量增加，但 rFGF1 并未导致肝糖原贮积病，因为 rFGF1 处理组的 GOT（谷草转氨酶）、GPT（谷丙转氨酶）降低和 SOD（超氧化物歧化酶）升高，导致肝炎症减轻，同时 il-1β、il-6 和 xbp-1 降低，nrf2 和肝细胞自噬体数量增加。肠道微生物和短链脂肪酸（SCFAs）发生变化，表明 rFGF1 使肠道乳杆菌、乙酸和丁酸水平显著升高。本研究探讨了 rFGF1 在高脂肪饮食喂养虹鳟模型中对葡萄糖代谢和炎症反应的分子机制，为改善肉食性鱼类的葡萄糖代谢调节提供了新的见解。
