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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)-1alpha and HIF-2alpha 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-1alpha-null (LHIF1alpha) and HIF-2alpha-null (LHIF2alpha) 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, LHIF1alpha and LHIF2alpha 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.

Type Journal
ISBN 1932-6203 (Electronic) 1932-6203 (Linking)
Authors Scott, C. H.; Cha, K. M.; Ngai, J.; Jiang, C.; Cheng, K.; Stokes, R. A.; Ho, K. W. K.; George, J.; Gonzalez, F. J.; Gunton, J. E.
Responsible Garvan Author Prof Jenny Gunton
Publisher Name PLoS One
Published Date 2017-11-30 00:00:00
Published Volume 12
Published Issue 11
Published Pages e0186543
Status ePublication
DOI 10.1371/journal.pone.0186543
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/29190746