硬骨魚在淡水酸化下獨特的產氨及能量代謝機制

Abstract

氣候變遷相關的環境酸化對地球上動物來說是個無法阻擋的災難。硬骨魚身為成功演化的水生脊椎動物被認為已經發展出有效率的策略以應對環境的酸化。當面對酸逆境時，哺乳類和硬骨魚都會活化排氨來排酸。然而，相較於哺乳類，硬骨魚是排氨動物 (ammonotelism)，主要倚賴鰓來排氨且其排氨量極大。硬骨魚不同哺乳類的代謝狀況也使他們可以做出更大程度的能量調度 (energy allocation)。根據上述，我們合理的假設排氨硬骨魚可能已經發展出獨特的機制以即時且有效率地應對酸、甚至適應酸性環境。日本青鱂魚 (Oryzias latipes) 作為本篇研究的實驗物種將被馴養於pH 4.5的淡水之中以驗證以上假說。 麩醯胺酸代謝是產氨作用 (ammoniagenesis) 的主要來源，而glutaminase (GLS) 調控的產氨作用也同樣地運作於哺乳類腎臟排氨的細胞中。在青鱂魚的鰓中，本研究出乎意料地發現了一群新型的、富含GLS的細胞 (GLS cells)，並大部分表現於排氨的離子細胞 (NHE cells) 旁。GLS cells可以執行完整的麩醯胺酸分解 (glutaminolysis) 且在酸化環境下被顯著的誘導。鰓上GLS cells和NHE cells的分工展現了不同於人類腎臟的近曲小管的機制，也讓青鱂魚的鰓在面對酸逆境時快速且有效率地活化排氨。 酸性環境下，青鱂魚多個器官的產氨作用改變了代謝的恆定，造成了器官間的能量調動。其中，肌肉、肝臟和卵巢有著最大的變化。在相對較低的基礎代謝下，被酸化的青鱂魚肌肉釋放氨基酸以支持全身的產氨。大量的代謝物也被肝臟吸收，透過促進脂肪合成作用 (lipogenesis) 和肝醣合成作用 (glycogenesis) 增加了青鱂魚的能量儲存。透過肝臟和卵巢間雌激素受體的訊息傳遞，青鱂魚進一步強化了生殖能力，而他們的子代成長也較快，指出環境酸化使青鱂魚有更好的適性 (fitness)。總結以上，青鱂魚在酸化環境下展現了一系列獨特且有效率的策略來對抗酸逆境。本研究不只完整呈現了硬骨魚在面對環境酸化的機制，也透過青鱂魚從生態的觀點上證明了一個經權衡後的能量調度。這些訊息對於精準預測硬骨魚在氣候變遷造成的環境酸化的生存和族群永續十分有價值。更多硬骨魚的物種正在等待被研究以支持本篇研究的發現。

Climate change-associated environmental acidification poses an unstoppable disaster for animals on Earth. As the successfully evolved aquatic vertebrates, teleosts are believed to have developed efficient strategies to cope with environmental acidification. When facing acidic stress, both mammals and teleosts activate ammonia excretion to eliminate acid. However, teleosts are ammonotelism, mainly using the gills for ammonia excretion and excreting a great amount of ammonia than mammals. The differential metabolism of teleosts from mammals also give them a greater extent of energy allocation. Accordingly, it is reasonable to assume that ammonotelic teleosts may have a unique mechanisms to timely and efficiently cope with acid and even adapt to acidic environments. In this study, Japanese medaka (Oryzias latipes) acclimated to pH 4.5 fresh water (FW) was used as the experimental model to validate the hypotheses. Glutamine metabolism serves as a main source of ammoniagenesis, and GLS-mediated ammoniagenesis is functioned in the ammonia-excreting cells of mammalian kidney. In medaka gills, surprisingly, the present study identified novel glutaminase (GLS)-rich cells (GLS cells), which were mostly nearby the ammonia-excreting Na+/H+ exchanger (NHE) cells. GLS cells conducted an entire process of glutaminolysis and were induced under acidic environments. The unique labor division of GLS and NHE cells demonstrates distinct mechanisms compared with those of the proximal tubular cells in human kidney. This unique trait also enables medaka gills to enhance ammonia excretion promptly and efficiently upon exposure of acidic stress. Systemic ammoniagenesis altered metabolic homeostasis, resulting in inter-organ energy mobilization in medaka under acidic environments. Among the organs, the muscle, liver, and ovary showed the most significant changes. Under relatively lower basal metabolic rate, medaka muscle released the amino acids to support systemic ammoniagenesis during acidic stress. The abundant metabolites were absorbed by the liver, which increased medaka energy storage by activating lipogenesis and glycogenesis. With the up-regulation of estrogen receptor (Esr) signaling between the liver and ovary, medaka ultimately enhanced reproductive activities, and their offspring grew faster, indicating the improved fitness of medaka under environmental acidification. To sum up, medaka showed a series of unique and efficient strategies to overcome acidic stress. The present study not only revealed comprehensive mechanisms in teleosts under acidic environments, but also demonstrates a trade-off energy allocation from an ecological perspective through acidified medaka. This information is valuable for precisely predicting the survival and population sustainability of teleosts under environmental acidification caused by climate changes. Further studies on additional teleostean species are eagerly awaited to support our finding.