透過特定脂肪訊號調控線蟲脂肪代謝及神經活性

Abstract

脂肪對於大部分的生物體是必要存在的物質，它不止提供生存所需能量還是一個重要的調控因子。在脂肪分解的過程中，脂肪酸會被游離出來變成游離脂肪酸 (Free fatty acids)，而游離脂肪酸和其衍生物已被知道可當作訊號因子去調控基因轉錄啟動與酵素活化。但對於飲食影響而產生的脂肪訊號因子如何去影響生物體功能，我們所知卻還是很少。我們實驗室以線蟲 (C. elegans)當作模式生物並餵食不同的細菌來研究飲食對於生物體的影響。在我們實驗室過去的研究中，發現線蟲在餵食不同飲食的狀況下，線蟲的生物體表現在脂肪含量和移動性相當不一樣。為了剖析差異中的分子機轉，我們使用了氣相層析質譜儀 (GC-MS)和液相層析質譜 (LC-MS)來分析線蟲和所食用的細菌。另外我們也採用阻斷線蟲產生這些游離脂肪酸以及外加游離脂肪酸的方法來探討其在線蟲中的功能。我們發現在特定的飲食餵食下特別的長碳鏈脂肪酸會影響線蟲內酸性胞器數目。另外也發現在特定飲食餵食下的突變線蟲可以回復神經傳遞物質的活性以及身體大小。而有些參與在脂肪代謝的酵素在不同飲食下基因轉錄表現也不同，其顯示飲食可能透過基因轉錄來調控線蟲脂肪組成和生理現象。總結來說，我們的實驗結果呈現了飲食上的差異會影響生物體脂質組成進而產生不同的脂質訊號分子並改變生物體的生理變化。

Lipids are important for cellular and physiological functions. Emerging evidences show that lipids not only provide energy but also play regulatory and signaling roles in multiple cellular processes. During lipid breakdown, the released free fatty acids (FFA) or resultant lipid derivatives have been shown to function as signaling molecules to regulate gene transcriptional activation and as co-activators to control enzyme activities. Still, little is known about how diets may be involved in lipid signaling to regulate host physiology. In our lab, we used C. elegans as a modal organism and fed them on different diets to study the dietary effects on C. elegans physiology. Our previous data indicated that C. elegans on different diets showed several physiological changes, including lipid content and locomotion. To dissect the mechanisms, we performed lipodomic analyses using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) approaches to identify variations in lipid compositions among bacteria and C. elegans fed on them. In addition, we examined the effects of the lipid compositions in bacteria and C. elegans may impact on C. elegans phenotypic changes by genetic mutations and lipid supplementation experiments. We found specific PUFAs that control the intestinal acidic organelles numbers of C. elegans fed on one but not the other bacterial diets. In addition, we found that some bacterial diet can rescue the phenotypes of uncoordinated movement and small body size in a mutant defective in lipid metabolism. Moreover, we found some genes involved in lipid metabolism are differentially expressed in worms fed on different diets, indicating that diets may modulate lipid composition and physiology through transcriptional regulation of these genes. Together, our results revealed that diets could impact lipidome within the organism, modulating lipid signaling molecules which may result in alteration in lifespan, locomotion, lipid contents etc.