Strategies to increase local T3 availability in liver (P16)

T3是肝脂代谢的关键调节因子。甲状腺功能减退与非酒精性(肥胖/糖尿病相关)肝骨病及其后遗症有关。我们的目标是通过使用选择性脱碘酶(DIO)同工酶抑制剂来控制肝细胞中降解T3的脱碘酶同工酶的活性，从而提高局部的T3浓度。局部的T3效应将通过在泰国小鼠来源的原代肝细胞培养和HiPSC来源的肝细胞系中表达的T3敏感报告结构来监测。

T3 is a key regulator of hepatic lipid metabolism. Hypothyroidism has been linked to non-alcoholic (obesity-/ diabetes-associated) hepatosteatosis and its sequelae. We aim to elevate local T3 concentrations by steering activities of T3-degrading deiodinase isozymes in hepatocytes by using selective deiodinase (DIO) isozyme inhibitors. Local T3 effects will be monitored by T3-sensitive reporter constructs expressed in THAI mouse-derived primary hepatocyte cultures and hiPSC-derived hepatocyte cell lines.