SLC13A3的缺失影響了老鼠的脂肪代謝而非認知功能

Abstract

果蠅的長壽基因I’m Not Dead Yet (INDY)和哺乳動物裡的其中一個同源基因Solute carrier family 13, member 5 (SLC13A5)會轉譯出位於細胞膜上的二羧酸與三羧酸通道蛋白。這兩個基因已被科學家進行多次研究，發現這兩個基因的缺失會影響脂肪代謝、胰島素的訊息傳遞、能量的平衡、和肥胖。然而，另一個INDY在哺乳動物的同源基因Solute carrier family 13, member 3 (SLC13A3)雖然能夠運送較多種三羧酸循環中的中間產物，過去卻沒有研究針對此基因在腦功能和代謝上的影響。在我的研究中，我會藉由比較野生型老鼠(wild type mice)和SLC13A3剔除的老鼠(SLC13A3 knockout mice) 來觀察兩者在認知功能和代謝上的差異。我發現在老鼠身上剃除SLC13A3會降低牠們的體重，這可能是因為此基因的剃除會促進牠們能量的使用、減少身上脂肪的堆積，和降低肝臟中脂肪的合成。但是，我沒有發現到基因剃除會影響腦和腎臟的功能。這些結果顯示出SLC13A3能夠作為一個很好的研究對象來研究脂肪代謝機制，也可能在未來提供了具有潛力的策略來治療肥胖和非酒精性脂肪肝疾病。

The life-extending gene I’m Not Dead Yet (INDY) in Drosophila and one of its mammalian homologs called Solute carrier family 13, member 5 (SLC13A5) encode di- and tri-carboxylate transporters on the plasma membrane and they have been highly investigated previously. Dysfunction of these genes would influence lipid metabolism, insulin signaling, energy balancing, brain, and obesity. However, another mammalian homolog of INDY called Solute carrier family 13, member 3 (SLC13A3), which could transport a wide range of intermediates in tricarboxylate cycle, has not been highly investigated for their functions on brain and metabolism. In this study, we compared SLC13A3 knockout mice with wild type mice to evaluate the changes in metabolism and brain functions. We found that the loss of SLC13A3 in mice could reduce their body weight. This may be due to their increased energy expenditure, the reduced accumulation of lipid, and the downregulation of the lipogenesis genes in the liver. However, the loss of SLC13A3 did not affect the normal function of brain and the kidney. These results show that SLC13A3 may be a great target for scientists to investigate the detailed mechanism of lipid metabolism and it might provide a potential way for the treatment of obesity and non-alcoholic fatty liver disease (NAFLD) in the future.