Structural analysis identifies an escape route from the adverse lipogenic effects of liver X receptor ligands.

ABSTRACT: Liver X receptors (LXRs) are attractive drug targets for cardiovascular disease treatment due to their role in regulating cholesterol homeostasis and immunity. The anti-atherogenic properties of LXRs have prompted development of synthetic ligands, but these cause major adverse effects-such as increased lipogenesis-which are challenging to dissect from their beneficial activities. Here we show that LXR compounds displaying diverse functional responses in animal models induce distinct receptor conformations. Combination of hydrogen/deuterium exchange mass spectrometry and multivariate analysis allowed identification of LXR regions differentially correlating with anti-atherogenic and lipogenic activities of ligands. We show that lipogenic compounds stabilize active states of LXRα and LXRβ whi

SUBMITTER: Belorusova AY 

PROVIDER: S-EPMC6874530 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature