Talarico Giancarlo G M, Farhat Elie, Mennigen Jan A, Weber Jean-Michel
Biology Department, University of Ottawa, Ottawa, Ontario, Canada.
Am J Physiol Regul Integr Comp Physiol. 2025 Mar 1;328(3):R306-R318. doi: 10.1152/ajpregu.00170.2024. Epub 2025 Jan 31.
The impact of hyperlipidemia on fuel selection has never been investigated in fish. This study quantifies how intralipid administration affects ) in vivo mobilization of lipids (lipolytic rate: glycerol) and carbohydrates (hepatic glucose production: glucose) in rainbow trout and ) key proteins involved in the regulation of fuel metabolism that could explain changes in glycerol and glucose kinetics. Results show that intralipid triples lipolytic rate (from 2.5 ± 0.5 to 7.8 ± 1.1 µmol glycerol kg·min) and inhibits glucose production by 36% (from 7.3 ± 0.9 to 4.7 ± 0.4 µmol kg·min). The stimulation of lipolysis is probably driven by lipase activation (gene expression of hormone-sensitive lipase increases in muscle) or by mass action effect. Such a strong lipolytic response is quite surprising because baseline glycerol is already particularly high in fish and is well known for its stability under a variety of stresses that have important effects in mammals. The reduction in trout glucose is likely caused by a large decrease in glycogen mobilization because hepatic gluconeogenic pathway capacity may rise as a consequence of increases in gluconeogenesis gene transcript levels. In contrast to humans, which maintain steady glucose production in response to intralipid infusion, rainbow trout appears to overcompensate increased gluconeogenic capacity with a disproportionately large inhibition of glycogen breakdown. Overall, these intralipid-driven changes in glycerol and glucose kinetics allow fish to decrease their reliance on carbohydrates and amino acids by replacing them, in part, with fatty acids as metabolic fuels. How do fish respond to an intralipid infusion (a soybean-derived emulsion used for parenteral nutrition of human patients)? In rainbow trout, intralipid administration triples the rate of lipid mobilization (lipolysis) and reduces hepatic glucose production by 36%. These changes in substrate fluxes allow fish to decrease their reliance on amino acids and carbohydrates by substituting them with fatty acids as metabolic fuels.
高脂血症对鱼类燃料选择的影响从未被研究过。本研究量化了静脉输注脂肪乳剂如何影响虹鳟鱼体内脂质的动员（脂解速率：甘油）和碳水化合物（肝脏葡萄糖生成：葡萄糖），以及参与燃料代谢调节的关键蛋白质，这些蛋白质可以解释甘油和葡萄糖动力学的变化。结果表明，静脉输注脂肪乳剂使脂解速率增加两倍（从2.5±0.5微摩尔甘油/千克·分钟增加到7.8±1.1微摩尔甘油/千克·分钟），并使葡萄糖生成减少36%（从7.3±0.9微摩尔/千克·分钟减少到4.7±0.4微摩尔/千克·分钟）。脂解的刺激可能是由脂肪酶激活（肌肉中激素敏感性脂肪酶的基因表达增加）或质量作用效应驱动的。如此强烈的脂解反应相当令人惊讶，因为鱼类的基础甘油水平已经特别高，并且在各种对哺乳动物有重要影响的应激下其稳定性是众所周知的。虹鳟鱼葡萄糖的减少可能是由于糖原动员大幅下降，因为肝脏糖异生途径能力可能会因糖异生基因转录水平的增加而提高。与人类在静脉输注脂肪乳剂时维持稳定的葡萄糖生成不同，虹鳟鱼似乎通过对糖原分解的不成比例的大幅抑制来过度补偿增加的糖异生能力。总体而言,这些由静脉输注脂肪乳剂驱动的甘油和葡萄糖动力学变化使鱼类能够减少对碳水化合物和氨基酸的依赖，部分地用脂肪酸替代它们作为代谢燃料。鱼类如何对静脉输注脂肪乳剂（一种用于人类患者肠外营养的大豆衍生乳剂）做出反应？在虹鳟鱼中，静脉输注脂肪乳剂使脂质动员（脂解）速率增加两倍，并使肝脏葡萄糖生成减少36%。底物通量的这些变化使鱼类能够减少对氨基酸和碳水化合物的依赖，用脂肪酸替代它们作为代谢燃料。
