Open AccessHepatic Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) regulates metabolism in mice
Author(s) -
Carolyn D. Scott,
Kuan-Minn Cha,
Jason Ngai,
Changtao Jiang,
Kui Cheng,
Rebecca Stokes,
Kenneth Ho,
Jacob George,
Frank J. Gonzalez,
Jenny E. Gunton
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0186543
Subject(s) - aryl hydrocarbon receptor nuclear translocator , endocrinology , medicine , aryl hydrocarbon receptor , biology , hypertriglyceridemia , glucose homeostasis , hypoxia (environmental) , chemistry , biochemistry , insulin resistance , diabetes mellitus , triglyceride , cholesterol , transcription factor , organic chemistry , oxygen , gene
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.