Multidrug Resistance Like Protein 1 Activity in Malpighian Tubules Regulates Lipid Homeostasis in .

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.