Endothelial force sensing signals to parenchymal cells to regulate bile and plasma lipids.

ABSTRACT: How cardiovascular activity interacts with lipid homeostasis is incompletely understood. We postulated a role for blood flow acting at endothelium in lipid regulatory organs. Transcriptome analysis was performed on livers from mice engineered for deletion of the flow-sensing PIEZO1 channel in endothelium. This revealed unique up-regulation of Cyp7a1, which encodes the rate-limiting enzyme for bile synthesis from cholesterol in hepatocytes. Consistent with this effect were increased gallbladder and plasma bile acids and lowered hepatic and plasma cholesterol. Elevated portal fluid flow acting via endothelial PIEZO1 and genetically enhanced PIEZO1 conversely suppressed Cyp7a1. Activation of hepatic endothelial PIEZO1 channels promoted phosphorylation of nitric oxide synthase 3,

SUBMITTER: Lichtenstein L 

PROVIDER: S-EPMC11430402 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature