The effect of Drosophila diacylglycerol lipase, inaE, on longevity and lipid metabolism in Drosophila

果蠅二醯甘油酯脂解酶對果蠅壽命以及脂肪代謝的影響

游琳圭(Lin-Kwei Yu)

指導教授 ： 汪宏達

國立清華大學/生命科學院/生物科技研究所/碩士(2009年)

摘要

Longevity is often associated with increased resistance to environmental stresses.
The screening for mutants that exhibit better resistance to oxidative stress leads to the
discovery of EP1101, which displays an enhanced lifespan. The P element of EP1101
inserts at 5’UTR of inaE, inactivation no afterpotential E (CG33174), a
diacylglycerol lipase (DAGL), which results in inaE over-expression. DAGL, a
mediator in mammalian endocannabinoid system, hydrolyzes diacylglycerol (DAG)
to generate 2-arachidonoylglycerol (2AG). The endocannabinoid system has been
shown to play an important role in lipid metabolism through the level of 2AG and
type 1 cannabinoid receptor (CB1) activity. Although there are no endocannabinoid
system and CB1 homologue found in Drosophila yet, we showed that the level of
triacylglycerol (TG) and the size of fat body cells are reduced in EP1101 compared to
the control, suggesting that inaE plays a role in lipid metabolism in Drosophila. The
over-expression of inaE may facilitate the conversion of DAG to 2AG, and in turn
may have less phosphatidic acid for TOR (target of rapamycin) signaling to influence
longevity and metabolism. The levels of phosphorylated eIF4E-binding protein (4EBP)
and S6 kinase (S6K), key components of TOR pathway, were decreased in EP1101
compared to the control. Together, we suggest that inaE over-expression regulates
DAG metabolism and results in reduced TOR signaling activity to enhance longevity
in Drosophila.

關鍵字

lipase ； longevity ； lipid metabolism

並列摘要

壽命長短常與能否抵抗環境中的種種壓力相關，其中包含飢餓、氧化壓力、
高溫。而在篩選可抵抗多重壓力的突變株果蠅時，我們發現了一株突變果蠅
EP1101 具有良好的氧化壓力及較長的壽命。EP1101 的 P element 安插於
inactivation no afterpotential E (inaE) 的5’端，導致inaE 的大量表現。inaE 為
哺乳類二酸甘油酯水解酶的同源基因，可以將二酸甘油酯水解為 2-花生四烯酸
甘油酯。在哺乳類動物的內生性類大麻系統內發現 2-花生四烯酸甘油酯會與大
麻鹼受體結合，影響脂肪的新陳代謝。雖然在果蠅中沒有內生性類大麻系統，也
還沒有發現大麻鹼受體的同源基因，但我們發現大量表現 inaE 在果蠅身上時，
可以降低三酸甘油酯的含量，且減少脂肪堆積，這表示 inaE 在果蠅中可能也參
與了脂肪的新陳代謝。而大量表現 inaE 也減少了二酸甘油酯的另一個磷酸化產
物-磷脂酸，而其可以活化雷帕黴素受器（TOR）。我們發現EP1101中，雷帕黴素
受器下游產物-S6 激酶和真核引發因子 4E 結合蛋白的磷酸化都有減少的趨勢。
我們認為大量表現inaE 可能是藉由降低雷帕黴素受器的活性使果蠅壽命增長。

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