Chen Jianxiang, Song Changyou, Wen Haibo, Liu Guangxiang, Wu Ningyuan, Li Hongxia, Xue Miaomiao, Xu Pao
Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China.
Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China.
Metabolites. 2022 Jul 27;12(8):697. doi: 10.3390/metabo12080697.
Our previous study demonstrated that low temperature could induce hepatic inflammation and suppress the immune and oxidation resistance of freshwater drum. However, the metabolism, especially the glucose and lipid metabolism involved, is poorly studied. To further explore the chronic hypothermia response of freshwater drum, an 8-day hypothermia experiment was conducted at 10 °C to investigate the effect of chronic hypothermia on glucose and lipid metabolism via biochemical and physiological indexes, and metabolic enzyme activities, miRNAs and mRNA-miRNA integrate analysis in the liver. Plasma and hepatic biochemical parameters reveal chronic hypothermia-promoted energy expenditure. Metabolic enzyme levels uncover that glycolysis was enhanced but lipid metabolism was suppressed. Differentially expressed miRNAs induced by hypothermia were mainly involved in glucose and lipid metabolism, programmed cell death, disease, and cancerization. Specifically, KEGG enrichment indicates that AMPK signaling was dysregulated. mRNA-miRNA integrated analysis manifests miR-1 and AMPK, which were actively co-related in the regulatory network. Furthermore, transcriptional expression of key genes demonstrates hypothermia-activated AMPK signaling by miR-1 and subsequently inhibited the downstream glucogenic and glycogenic gene expression and gene expression of fatty acid synthesis. However, glycogenesis was alleviated to the control level while fatty acid synthesis was still suppressed at 8 d. Meanwhile, the gene expressions of glycolysis and fatty acid oxidation were augmented under hypothermia. In conclusion, these results suggest that miR-1/AMPK is an important target for chronic hypothermia control. It provides a theoretical basis for hypothermia resistance on freshwater drum.
我们之前的研究表明，低温可诱导淡水鼓肝脏炎症，并抑制其免疫和抗氧化能力。然而，关于其代谢，尤其是涉及的葡萄糖和脂质代谢的研究较少。为了进一步探究淡水鼓对慢性低温的反应，在10℃下进行了为期8天的低温实验，通过生化和生理指标、代谢酶活性、miRNA以及肝脏中的mRNA-miRNA整合分析，研究慢性低温对葡萄糖和脂质代谢的影响。血浆和肝脏生化参数显示慢性低温促进了能量消耗。代谢酶水平表明糖酵解增强但脂质代谢受到抑制。低温诱导的差异表达miRNA主要参与葡萄糖和脂质代谢、程序性细胞死亡、疾病和癌变。具体而言，KEGG富集表明AMPK信号通路失调。mRNA-miRNA整合分析表明miR-1与AMPK在调控网络中存在积极的共相关关系。此外，关键基因的转录表达表明低温通过miR-1激活AMPK信号通路，随后抑制下游糖异生和糖原生成基因表达以及脂肪酸合成基因表达。然而，糖原生成在第8天时恢复到对照水平，而脂肪酸合成仍受到抑制。同时，低温下糖酵解和脂肪酸氧化的基因表达增加。总之，这些结果表明miR-1/AMPK是慢性低温调控的重要靶点。它为淡水鼓的抗低温能力提供了理论依据。
