Human germline hedgehog pathway mutations predispose to fatty liver.

ABSTRACT:

Background & aims

Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations that affect this pathway.

Methods

Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD. A combined mouse model of Hh signaling attenuation (Gli2 heterozygous null: Gli2^+/-) and diet-induced NAFLD was used to examine aspects of NAFLD and hepatic gene expression profiles, including molecular markers of hepatic fibrosis and inflammati

SUBMITTER: Guillen-Sacoto MJ 

PROVIDER: S-EPMC5613974 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature