演題：A Novel BAT-derived Pro-Fibrotic Protein Promotes Pathogenesis in 　

　　　Cardiovascular-Metabolic Diseases

演者：蕭 詠庭

　　　国立循環器病研究センター 心血管老化制御部　上級研究員

抄録：

　Aging and lifestyle-related diseases, including obesity, enhance cardiac, liver, and renal fibrosis and become the major risk factors for heart failure with preserved ejection fraction (HFpEF), Metabolic dysfunction-associated steatohepatitis (MASH), and chronic kidney disease (CKD). Previous studies tested the therapeutic potential of white adipose tissue (WAT)-derived senescence-associated secretory phenotype (SASP) factors in metabolic disorders, showing various results depending on the targeted molecules or diseases. Brown adipose tissue (BAT) is another type of fat pad equipped with the thermogenic capacity, and the role of BAT-derived adipokines (BATokines) in the pathogenesis of MASH, HFpEF, and CKD remains to be explored. Here we identified a secreted type of pro-fibrotic protein, PCPE-1, as one of the BATokines contributing to the promotion of liver, heart fibrosis in murine obese and aging models, and unilateral ureteral obstruction (UUO)-induced CKD model, but also found that the circulating PCPE-1 levels were increased in human MASH, HFpEF, and CKD patients. Genetic models with PCPE-1 suppression ameliorated liver, heart, and renal fibrosis. In vitro studies showed that PCPE-1 was up-regulated through reactive oxygen species (ROS)/ DNA damage/ c-fos/ c-jun pathways in brown adipocytes. Our results indicate that suppressing PCPE-1 could be a therapy for HFpEF, MASH, and CKD development.

日　時：2025年7月4日（金）16：00 〜 17：00

場　所：研究所3階　332号室