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Md Nurul Islam Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Yuichiro Mita Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
Systems Life Sciences Laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyoto, Japan

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Keisuke Maruyama Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Ryota Tanida Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
Department of Sports and Fitness, Faculty of Wellness, Shigakkan University, Aichi, Japan

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Weidong Zhang Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Hideyuki Sakoda Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Masamitsu Nakazato Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
CREST (Japan) Agency for Medical Research and Development (A-MED) 1-7-1 Otemachi, Tokyo, Japan

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al. 2001 , Zigman et al. 2006 ). Liver-expressed antimicrobial peptide 2 (LEAP2), a 40 amino acid peptide, was originally isolated by comprehensive chromatographic characterization of human hemofiltrate ( Krause et al. 2003 ). Human LEAP2 is

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Flávia Maria Silva-Veiga Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil

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Carolline Santos Miranda Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil

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Fabiane Ferreira Martins Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil

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Julio Beltrame Daleprane Laboratory for Studies of Interactions between Nutrition and Genetics, LEING, Institute of Nutrition, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil

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Carlos Alberto Mandarim-de-Lacerda Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil

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Vanessa Souza-Mello Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil

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health. Fructose intake has increased in recent years due to ultra-processed food intake and causes lipotoxicity with ectopic lipid deposition ( Lambertz et al. 2017 ). Non-alcoholic fatty liver disease (NAFLD) is characterized by intrahepatic lipid

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Joëlle Dupont PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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Sophie Tesseraud PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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Michel Derouet PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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Anne Collin PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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Nicole Rideau PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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Sabine Crochet PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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Estelle Godet PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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Estelle Cailleau-Audouin PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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Sonia Métayer-Coustard PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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Michel J Duclos PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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Christian Gespach PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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Tom E Porter PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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Larry A Cogburn PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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Jean Simon PRC (UMR 6175), Station de Recherches Avicoles (UR 83), INSERM, Department of Animal and Avian Sciences, Department of Animal and Food Sciences, INRA, 37380 Nouzilly, France

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). Tyrosine phosphorylation of IR β-subunit, IRS-1 and Shc, and phosphatidylinositol 3-kinase (PI3K) activity appeared responsive to insulin status in the liver under several experimental conditions (fasting/re-feeding, chronic corticosterone treatment

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Emma Rose McGlone Department of Surgery and Cancer, Imperial College London, London, UK

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Stephen R Bloom Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK

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Tricia M-M Tan Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK

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Introduction Glucagon is a peptide hormone secreted by alpha cells in the pancreas which acts on several organs including the liver, kidney, heart and brain ( Marroqui et al. 2014 , Wewer Albrechtsen et al. 2023 ). The precursor protein

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Susan Kralisch Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany

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Anke Tönjes Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany

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Kerstin Krause Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany

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Judit Richter Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany

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Ulrike Lossner Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany

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Peter Kovacs Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany

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Thomas Ebert Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany

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Matthias Blüher Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany

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Michael Stumvoll Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany

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Mathias Fasshauer Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany

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Introduction Fibroblast growth factor-21 (FGF21) is a member of the FGF family including 22 members ( Beenken & Mohammadi 2009 ). FGF21 is mainly produced by the liver but also by other tissues including white adipose tissue (WAT), skeletal muscle

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Shui-lin Sun Department of Infection, Second Affiliated Hospital of Nanchang University, Nanchang, China

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Liang-ming Liu Department of Infection, Songjiang Hospital Affiliated to First People’s Hospital, Shanghai Jiaotong University, Shanghai, China

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distributed in animal organs and tissues. Many organs, including the cardiovascular and central nervous systems, as well as the lung, kidney, spleen, hypophysis, adrenal gland, stomach, pancreas, ovary and liver, are found to express UII ( Coulouarn et al

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Marcos Divino Ferreira-Junior Laboratory of Endocrine Physiology and Metabolism, Department of Physiological Sciences, Federal University of Goias, Goiânia, Brazil
Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal

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Keilah Valéria Naves Cavalcante Laboratory of Endocrine Physiology and Metabolism, Department of Physiological Sciences, Federal University of Goias, Goiânia, Brazil

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Carlos Henrique Xavier Systems Neurobiology Laboratory, Department of Physiological Sciences, Federal University of Goias, Goiânia, Brazil

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Emerielle Cristine Vanzela Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil

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Antonio Carlos Boschero Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil

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Paulo Matafome University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal
University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal
Clinical and Academic Centre of Coimbra (CACC), Coimbra, Portugal
Polytechnic University of Coimbra, Coimbra Health School, H&T Research Center, Coimbra, Portugal

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Rodrigo Mello Gomes Laboratory of Endocrine Physiology and Metabolism, Department of Physiological Sciences, Federal University of Goias, Goiânia, Brazil
Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil

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, different from other G-protein-coupled receptors ( Damian et al. 2012 ). Conformational analyses demonstrated the ability of liver-expressed antimicrobial peptide 2 (LEAP2) to bind to GHSR as an inverse agonist, in view of the change in conformation

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Raquel Barbuio Department of Internal Medicine and Gastrocentro, State University of Campinas, Campinas, SP 13083–970, Brazil

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Marciane Milanski Department of Internal Medicine and Gastrocentro, State University of Campinas, Campinas, SP 13083–970, Brazil

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Manoel B Bertolo Department of Internal Medicine and Gastrocentro, State University of Campinas, Campinas, SP 13083–970, Brazil

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Mário J Saad Department of Internal Medicine and Gastrocentro, State University of Campinas, Campinas, SP 13083–970, Brazil

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Lício A Velloso Department of Internal Medicine and Gastrocentro, State University of Campinas, Campinas, SP 13083–970, Brazil

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Introduction Non-alcoholic fatty liver disease (NAFLD) comprehends a large spectrum of clinicopathological conditions of the liver, ranging from steatosis to cirrhosis, and including steatohepatitis (NASH) and fibrosis ( Browning

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Johan Svensson Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Göteborg, Sweden
Department of Clinical Physiology, Göteborg University, Göteborg, Sweden
Musculoskeletal Disease Center, Jerry L Pettis Memorial VA Medical Center, Loma Linda, California, USA
Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden

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Åsa Tivesten Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Göteborg, Sweden
Department of Clinical Physiology, Göteborg University, Göteborg, Sweden
Musculoskeletal Disease Center, Jerry L Pettis Memorial VA Medical Center, Loma Linda, California, USA
Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden

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Klara Sjögren Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Göteborg, Sweden
Department of Clinical Physiology, Göteborg University, Göteborg, Sweden
Musculoskeletal Disease Center, Jerry L Pettis Memorial VA Medical Center, Loma Linda, California, USA
Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden

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Olle Isaksson Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Göteborg, Sweden
Department of Clinical Physiology, Göteborg University, Göteborg, Sweden
Musculoskeletal Disease Center, Jerry L Pettis Memorial VA Medical Center, Loma Linda, California, USA
Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden

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Göran Bergström Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Göteborg, Sweden
Department of Clinical Physiology, Göteborg University, Göteborg, Sweden
Musculoskeletal Disease Center, Jerry L Pettis Memorial VA Medical Center, Loma Linda, California, USA
Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden

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Subburaman Mohan Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Göteborg, Sweden
Department of Clinical Physiology, Göteborg University, Göteborg, Sweden
Musculoskeletal Disease Center, Jerry L Pettis Memorial VA Medical Center, Loma Linda, California, USA
Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden

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Johan Mölne Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Göteborg, Sweden
Department of Clinical Physiology, Göteborg University, Göteborg, Sweden
Musculoskeletal Disease Center, Jerry L Pettis Memorial VA Medical Center, Loma Linda, California, USA
Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden

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Jörgen Isgaard Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Göteborg, Sweden
Department of Clinical Physiology, Göteborg University, Göteborg, Sweden
Musculoskeletal Disease Center, Jerry L Pettis Memorial VA Medical Center, Loma Linda, California, USA
Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden

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Claes Ohlsson Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Göteborg, Sweden
Department of Clinical Physiology, Göteborg University, Göteborg, Sweden
Musculoskeletal Disease Center, Jerry L Pettis Memorial VA Medical Center, Loma Linda, California, USA
Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden

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& Schaefer 2004 ). The major part of serum IGF-I is liver derived ( Sjögren et al. 1999 , Yakar et al. 1999 ). In addition to being regulated by GH ( Bengtsson et al. 1993 ), serum IGF-I levels are also affected by factors, such as food intake

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Julia N C Toews Department of Cellular & Physiological Sciences, The University of British Columbia, Vancouver, Canada

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Geoffrey L Hammond Department of Cellular & Physiological Sciences, The University of British Columbia, Vancouver, Canada

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Victor Viau Department of Cellular & Physiological Sciences, The University of British Columbia, Vancouver, Canada

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Introduction As a critical regulator of metabolic homeostasis, the liver senses and integrates hormone signals triggered by alterations in metabolism and/or physiological state in terrestrial vertebrates. Hepatocytes respond to these changes

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