Non-nucleoside reverse transcriptase inhibitor efavirenz activates PXR to induce hypercholesterolemia and hepatic steatosis.

ABSTRACT:

Background & aims

The most prescribed non-nucleoside reverse transcriptase inhibitor, efavirenz, has been associated with elevated risk of dyslipidemia and hepatic steatosis in HIV-infected patients but the underlying mechanisms remain elusive. Herein, we investigated the role of pregnane X receptor (PXR) in mediating the adverse effects of efavirenz on lipid homeostasis.

Methods

Cell-based reporter assays, primary cell culture, and multiple mouse models including conditional knockout and humanized mice were combined to study the impact of efavirenz on PXR activities and lipid homeostasis in vitro and in vivo. A novel liver-specific Pxr knockout mouse model was also generated to determine the contribution of hepatic PXR signaling to efavirenz-elicited dyslipidemia and hepati

SUBMITTER: Gwag T 

PROVIDER: S-EPMC6462244 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature