Liu Wen, Cao Hao, Kimari Moses, Maronitis Georgios, Williams Michael J, Schiöth Helgi B
Functional Pharmacology, Department of Neuroscience, Uppsala University, 751 24 Uppsala, Sweden.
Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
Membranes (Basel). 2021 Jun 8;11(6):432. doi: 10.3390/membranes11060432.
Multidrug resistance proteins (MRPs), members of the ATP-binding cassette transporter (ABC transporter) family, are pivotal for transporting endo- and xenobiotics, which confer resistance to anticancer agents and contribute to the clearance of oxidative products. However, their function in many biological processes is still unclear. We investigated the role of an evolutionarily conserved MRP in metabolic homeostasis by knocking down the expression of () in several tissues involved in regulating metabolism, including the gut, fat body, and Malpighian tubules. Interestingly, only suppression of in the Malpighian tubules, the functional equivalent to the human kidney, was sufficient to cause abnormal lipid accumulation and disrupt feeding behavior. Furthermore, reduced Malpighian tubule expression resulted in increased (homolog of human ) expression. is known to play a role in detoxification and lipid metabolism processes. Reduced expression of in the Malpighian tubules also conveyed resistance to oxidative stress, as well as reduced normal levels of reactive oxygen species in adult flies. This study reveals that an evolutionarily conserved MRP is required in Malpighian tubules for proper metabolic homeostasis.
多药耐药蛋白（MRPs）是ATP结合盒转运蛋白（ABC转运蛋白）家族的成员，对于内源性和外源性物质的转运至关重要，这些物质赋予了对抗癌药物的抗性并有助于清除氧化产物。然而，它们在许多生物学过程中的功能仍不清楚。我们通过敲低参与调节代谢的几个组织（包括肠道、脂肪体和马氏管）中（）的表达，研究了一种进化保守的MRP在代谢稳态中的作用。有趣的是，只有抑制马氏管（相当于人类肾脏的功能器官）中的（），就足以导致异常的脂质积累并扰乱摄食行为。此外，马氏管（）表达的降低导致（人类（）的同源物）表达增加。已知（）在解毒和脂质代谢过程中发挥作用。马氏管中（）表达的降低还使成年果蝇对氧化应激产生抗性，并降低了活性氧的正常水平。这项研究表明，马氏管中需要一种进化保守的MRP来维持适当的代谢稳态。
