細菌飲食經由表觀遺傳調控線蟲脂肪含量及生長速度

Abstract

脂肪代謝系統的異常與許多嚴重的疾病有關係，例如:肥胖症、心血管疾病及糖尿病。同時，脂肪的多寡在許多物種中對於生長發育也有一定程度的影響。雖然已經有許多關於脂肪代謝異常的問題的研究，但是飲食如何同時調控生長發育及改變脂肪代謝仍然未有進一步的解釋。在我的研究中，我們使用秀麗隱桿線蟲當作模式生物。我們餵食線蟲兩種不同的細菌--Comamonas DA1877 和 E. coli OP50，用以探討飲食如何去調控脂肪儲存及生長速度。先前研究發現當野生型線蟲(N2)餵食DA1877飲食時，會比餵食OP50這種標準食物脂肪含量來的少，並呈現生長加速現象。sams-1 是一個 合成S-adenosyl methionine (SAM)酵素。在我的研究中發現，當線蟲缺少sams-1後，雖然餵食DA1877或OP50，都會出現高脂肪含量及生長速度的減緩，且兩種食物的造成的效果差異不大，這使我們推測sams-1這個酵素應該參與在DA1877降低脂肪代謝和增加生長速度的途徑之中。為了瞭解這背後的機制，我們在缺乏sams-1的線蟲中補充其合成產物SAM，發現SAM的確會影響線蟲脂肪含量和生長速度，但是外SAM 並無法展現如同DA1877飲食的效果，因此我們推測sams-1在調控脂肪儲存和生長速度上，除了透過合成SAM外，應有另一條獨立於SAM合成的路徑。為了了解這個路徑，我們檢測SAMS-1基因究竟會表現在什麼位置。我們發現，在餵食兩種食物下，SAMS-1皆會表現在腸道(intestinal cells)及表皮細胞(hypodermal cells)中。尤其重要的是，SAMS-1會坐落在這些細胞的細胞核內。在哺乳類動物實驗上 SAMS-1的同源基因MAT II

Lipid contents are essential for developmental processes in many species. Dysregulation of lipid metabolism has been associated with many severe diseases, like obesity, cardiac dysfunction, and diabetes mellitus. Although lipid metabolism has been extensively studied, the relationship between diets, lipid content and developmental rate remains largely unknown. In our studies, we used C. elegans as the model organism and fed them bacteria Comamonas DA1877 or E. coli OP50 to investigate how diets regulate lipid content and developmental rate. Previous studies have shown that wild type worms had lower lipid content and accelerated developmental rate on DA1877 than OP50 diet. sams-1 is a S-adenosyl methionine (SAM) synthase gene which is reported to regulate lipid content. Our data revealed that, sams-1 deficiency worms exhibited high lipid content and decreased developmental rate on both diets. To understand its underlying mechanism, we supply SAM for sams-1 mutants. Results showed that SAM supplement affected lipid content and developmental rate. However a SAM supplement level could not mimic DA1877-mediated lipid reduction and developmental rate acceleration, suggesting that sams-1 has a SAM-synthesis dependent and independent role in regulation of lipid reduction and developmental rate. To understand SAM-synthesis independent pathway, we observed the localization of SAMS-1. We found that SAMS-1 is expressed in the intestinal and hypodermal cells in both diets. Specifically, SAMS-1 is localized in the nucleus of these cells. In mammals, MAT II