Shuwei Hu, Yingdong Zhu, Xiaojie Zhao, Rui Li, Guangze Shao, Dongxu Gong, Chencheng Hu, Hongjun Liu, Kexin Xu, Chenxi Liu, Minghuan Xu, Zhonghua Zhao, Tao Li, Zhigang Hu, Mengle Shao, Jun- Liu, Xinwei Li, Huijuan Wu, Jing Li, Yanyong Xu
High-density lipoprotein (HDL) metabolism is regulated by complex interplay between the scavenger receptor group B type 1 (SR-BI) and multiple signaling molecules in the liver. Here, we show that lipocalin-2 (Lcn2) is a key regulator of hepatic SR-BI, HDL metabolism, and atherosclerosis. Overexpression of human Lcn2 in hepatocytes attenuates the development of atherosclerosis via SR-BI in western-diet-fed Ldlr-/- mice, whereas hepatocyte-specific ablation of Lcn2 has the opposite effect. Mechanistically, hepatocyte Lcn2 improves HDL metabolism and alleviates atherogenesis by blocking Nedd4-1-mediated SR-BI ubiquitination at K500 and K508...
October 18, 2023: Developmental Cell