Receptor-interacting protein 1 and 3 kinase activity are required for high-fat diet induced liver injury in mice.

ABSTRACT:

Background

The RIP1-RIP3-MLKL-mediated cell death pathway is associated with progression of non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH). Previous work identified a critical role for MLKL, the key effector regulating necroptosis, but not RIP3, in mediating high fat diet-induced liver injury in mice. RIP1 and RIP3 have active N-terminus kinase domains essential for activation of MLKL and subsequent necroptosis. However, little is known regarding domain-specific roles of RIP1/RIP3 kinase in liver diseases. Here, we hypothesized that RIP1/RIP3 kinase activity are required for the development of high fat diet-induced liver injury.

Methods

Rip1^K45A/K45A and Rip3^K51A/K51A kinase-dead mice on a C57BL/6J background and their litt

SUBMITTER: Wu X 

PROVIDER: S-EPMC10757356 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature