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

Abstract

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. There was increased expression of G6Pase, Chrebp, Fas and Scd-1 mRNAs in LARNT animals. Surprisingly, LHIF1α and LHIF2α mice exhibited no alterations in any metabolic parameter assessed.

CONCLUSIONS:

These results provide convincing evidence that reduced hepatic ARNT can contribute to inappropriate hepatic glucose production and post-prandial dyslipidaemia. Hepatic ARNT may be a novel therapeutic target for improving post-prandial hypertriglyceridemia and glucose homeostasis.

• Authors: Christopher H Scott, Kuan-Minn Cha, Jason Ngai, Changtao Jiang, Kim Cheng, Rebecca A Stokes, Kenneth W K Ho, Jacob George, Frank J Gonzalez, Jenny E Gunton
• Journal: PloS one (PLoS One) Vol. 12 Issue 11 Pg. e0186543 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 29190746 (Publication Type: Journal Article)

Chemical References

• Arnt protein, mouse
• Basic Helix-Loop-Helix Transcription Factors
• Blood Glucose
• Hypoxia-Inducible Factor 1, alpha Subunit
• Aryl Hydrocarbon Receptor Nuclear Translocator
• endothelial PAS domain-containing protein 1
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Aryl Hydrocarbon Receptor Nuclear Translocator (genetics, physiology)
• Basic Helix-Loop-Helix Transcription Factors (genetics)
• Blood Glucose (metabolism)
• Energy Metabolism (physiology)
• Fasting
• Gene Deletion
• Gene Expression
• Glucose Tolerance Test
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics)
• Lipid Metabolism
• Liver (metabolism)
• Mice
• Phenotype