Hepatic Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) regulates metabolism in mice.

Background & Aims: Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) and its partners hypoxia-inducible factors (HIF)-1α and HIF-2α are candidate factors for the well-known link between the liver, metabolic dysfunction and elevation in circulating lipids and glucose. Methods: Hepatocyte-specific ARNT-null (LARNT), HIF-1α-null (LHIF1α) and HIF-2α-null (LHIF2α) mice were created.

Results: LARNT mice had increased fasting glucose, impaired glucose tolerance, increased glucose production, raised post-prandial serum triglycerides (TG) and markedly lower hepatic ATP versus littermate controls.

Novel links between HIFs, type 2 diabetes, and metabolic syndrome.

Hypoxia inducible factors (HIFs) are master-regulators of cellular responses to hypoxia, and thus are crucial for survival. HIFs also play a role in regulating cellular processes in β-cells, liver, muscle, and adipose tissue, have effects on the regulation of weight, and play a role in type 2 diabetes (T2D). Indeed, in people with T2D the HIF pathway is dyregulated in major metabolic tissues involved in the pathogenesis of diabetes.