在線蟲內飲食調控酸性鞘磷脂酶

Abstract

飲食深深的影響生物體的代謝平衡，而代謝平衡調節許多生理功能且與許多疾病成因有關，然而至今飲食如何調節生物的生理反應仍有待釐清，本研究利用秀麗桿線蟲作為模式生物去剖析飲食所致的代謝分子機制，其中包括脂質磷脂醯膽鹼(Phosphatidylcholine)的含量以及鞘脂(sphingolipid)穩定平衡的影響，另外，利用高通量核糖核酸測序(RNA-seq)分析線蟲在飲食影響下基因表現的調控，而發現一個調控鞘脂代謝基因具有飲食差異性的基因表現，因此我們創造此基因轉殖的線蟲去探討其對於飲食的反應，經過實驗測試後我們發現許多的轉錄因子參與這個基因的表現，其中特別是胰島素訊號路徑扮演一個重要的角色，他可能是透過調節DAF-16 入核去影響的基因表現，進而調控脂肪含量。再者，本研究發現該基因可以自我調節基因表現，其原因是透過影響磷脂醯膽鹼和鞘脂質相關代謝物而正回饋自己的基因表現，且其回饋反應可能是透過胰島素受體訊號路徑，簡而言之，飲食可以透過調節基因的表現去影響生物的代謝平衡，其代謝物又能影響飲食所調節的生理機制。

Diets profoundly influence organismal metabolism homeostasis, which affect numerous physiological processes and associate with various diseases. To date, how the diets regulate host physiological responses still remain elucidated. Here, we utilize Caenorhabditis elegans as a model organism to dissect the underlying molecular mechanisms about how diets impact on organismal metabolism homeostasis, including PC level and sphingolipid metabolism to affect lipid content. By analysis of RNA-seq data, we found a gene involved in sphingolipid metabolism is differentially expressed and generated transgenic worms to determine its impact on diets-mediated responses. After examination, we found several transcription factors participate in the regulation of this gene expression in response to different diets. Specifically, DAF-2/IIS signaling pathway plays an important role via inhibiting the nuclear localization of the Foxo transcription factor DAF-16 to regulate this gene expression and further affect lipid content level in animals. Moreover, we found that this gene could self-regulate its expression, possibly by feedback to DAF-2/IIS signaling. Altogether, diets could regulate organismal genes expression to influence host metabolism homeostasis and these metabolites alterations also contribute to diets-mediated responses.