The metabolic adaptation of bile acids and cholesterol after biliary atresia in lamprey via transcriptome-based analysis
Qipeng Zhang,
Jilong Pan,
Yingying Zhu,
Jindi Liu,
Yue Pang,
Jiarui Li,
Pengju Han,
Meng Gou,
Jun Li,
Peng Su,
Qingwei Li,
Yan Chi
Affiliations
Qipeng Zhang
College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China
Jilong Pan
College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China
Yingying Zhu
College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China
Jindi Liu
College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China
Yue Pang
College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China
Jiarui Li
College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China
Pengju Han
College of Life Sciences, Sichuan University, Sichuan, China
Meng Gou
College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China
Jun Li
College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China
Peng Su
College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China
Qingwei Li
College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China; Corresponding author. College of Life Sciences, Liaoning Normal University, Dalian 116081, China.
Yan Chi
College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China; Corresponding author. College of Life Sciences, Liaoning Normal University, Dalian 116081, China.
Lamprey underwent biliary atresia (BA) at its metamorphosis stage. In contrast to patients with BA who develop progressive disease, lamprey can grow and develop normally, suggesting that lamprey has several adaptations for BA. Here we show that adaptive changes in bile acid and cholesterol metabolism are produced after lamprey BA. Among 1102 differentially expressed genes (DGEs) after BA in lamprey, many are enriched in gene ontology (GO) terms and pathways related to steroid metabolism. We find that among the DGEs related to bile acids and cholesterol metabolism, the expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1), sodium-dependent taurine cotransport polypeptide (NTCP) are significantly downregulated, whereas nuclear receptor farnesoid X receptor (FXR), multidrug resistance-associated protein 3 (MRP3), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), sterol O-acyltransferase 1 (SOAT1), and ATP binding cassette subfamily A member 1 (ABCA1) are remarkably upregulated. The changes in expression level are also validated by RT-qPCR. Furthermore, the level of high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in juvenile serum is higher compared to larvae. Taken together, the findings collectively indicate that after BA, lamprey may maintain bile acids and cholesterol homeostasis in liver tissue by inhibiting bile acids synthesis and uptake, promoting its efflux back to circulation, and enhancing cholesterol esterification for storage as lipid droplets and its egress to form nascent HDL (nHDL). Understanding the possible molecular mechanisms of lamprey metabolic adaptation sheds new light on the understanding of the development and treatment of diseases caused by abnormal bile acid and cholesterol metabolism in humans.
