Systemic inactivation of hypoxia-inducible factor prolyl 4-hydroxylase 2 in mice protects from alcohol-induced fatty liver disease.

ABSTRACT: Alcoholic fatty liver disease (AFLD) is a growing health problem for which no targeted therapy is available. We set out to study whether systemic inactivation of the main hypoxia-inducible factor prolyl 4-hydroxylase, HIF-P4H-2 (PHD2/EglN1), whose inactivation has been associated with protection against metabolic dysfunction, could ameliorate it. HIF-P4H-2-deficient and wild-type (WT) mice or HIF-P4H inhibitor-treated WT mice were subjected to an ethanol diet for 3-4 weeks and their metabolic health, liver and white adipose tissue (WAT) were analyzed. Primary hepatocytes from the mice were used to study cellular ethanol metabolism. The HIF-P4H-2-deficient mice retained a healthier metabolic profile, including less adiposity, better lipoprotein profile and restored insulin sensitivity, whil

SUBMITTER: Laitakari A 

PROVIDER: S-EPMC6396018 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature