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Manuel Gado Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany

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Eva Tsaousidou Sabri Ülker Center for Metabolic Research, Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA

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Stefan R Bornstein Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
Diabetes and Nutritional Sciences, King's College London, London, UK

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Nikolaos Perakakis Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany

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Introduction: pathogenesis of insulin resistance Insulin resistance is defined as the inadequate response of tissues, such as adipose tissue, skeletal muscle, central nervous system, and liver, to insulin. Insulin resistance and impaired

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Amanda J Genders Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Jujiao Kuang Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Evelyn C Marin Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Nicholas J Saner Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Javier Botella Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Macsue Jacques Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Glenn K McConell Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Victor A Andrade-Souza Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Javier Chagolla Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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David J Bishop Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Introduction Patients with insulin resistance have been reported to have decreased skeletal muscle mitochondrial content ( Kelley et al. 2002 , Ritov et al. 2005 , Chomentowski et al. 2011 ) and reductions in skeletal muscle

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Gencer Sancar German Center for Diabetes Research, Neuherberg, Germany
Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany
Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany

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Andreas L Birkenfeld German Center for Diabetes Research, Neuherberg, Germany
Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany
Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany

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metabolic disturbances is insulin resistance, which is a condition in which the body's cells become resistant to the effects of insulin, leading to impaired glucose and lipid homeostasis. Adipose tissue dysfunction plays a crucial role in the development of

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Sandra Pereira Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Anu Shah Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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I George Fantus Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Jamie W Joseph Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Adria Giacca Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Introduction Obesity is associated with elevated circulating free fatty acids (FFAs) and FFAs cause insulin resistance ( Lewis et al . 2002 , Xiao et al . 2008 ). FFAs induce oxidative stress ( Nakamura et al . 2009 , Yuzefovych et al . 2010

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Jiean Xu State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Qiuhua Yang State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Xiaoyu Zhang State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Zhiping Liu State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Yapeng Cao State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Lina Wang State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Yaqi Zhou State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Xianqiu Zeng State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Qian Ma State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Yiming Xu Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China

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Yong Wang Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China

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Lei Huang Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, China

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Zhen Han Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, China

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Tao Wang Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, China

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David Stepp Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Zsolt Bagi Department of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Chaodong Wu Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Mei Hong State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China

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Yuqing Huo Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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resistance-associated metabolic perturbations. Accumulating evidence highlights a critical role for adenosine signaling in the development of insulin resistance ( Antonioli et al. 2015 , Pardo et al. 2017 ). Adenosine signaling is also closely

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Mohamed Asrih Service of Endocrinology, Diabetes, Hypertension and Nutrition, Geneva University Hospital, Rue Gabrielle‐Perret‐Gentil 4, 1211 Genève 14, Switzerland

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François R Jornayvaz Service of Endocrinology, Diabetes, Hypertension and Nutrition, Geneva University Hospital, Rue Gabrielle‐Perret‐Gentil 4, 1211 Genève 14, Switzerland

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, insulin resistance, hypertension, and dyslipidemia, suggesting that NAFLD might be considered as the liver manifestation of the metabolic syndrome ( Marchesini et al . 2001 , Adams et al . 2005 ). The metabolic syndrome is a leading cause of mortality

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Qiuhua Yang Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Jiean Xu Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Qian Ma Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Zhiping Liu Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Yaqi Zhou State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University, Shenzhen, China

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Yongfeng Cai State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University, Shenzhen, China

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Xiaoxiao Mao Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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David Stepp Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Neal Weintraub Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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David J Fulton Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Mei Hong State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University, Shenzhen, China

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Yuqing Huo Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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-fat diet (HFD)-induced insulin resistance. Saturated fatty acids are major contributors to the process of high-fat feeding, causing insulin resistance ( Nakamura et al. 2009 ). It has been well demonstrated that palmitate induces inflammation in

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Xiao-Bing Cui Department of Physiology and Pharmacology, Renmin Hospital, Antioxidant and Gene Regulation Laboratory, University of Georgia, 501 D.W. Brooks Drive, Athens, Georgia 30602, USA

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Jun-Na Luan Department of Physiology and Pharmacology, Renmin Hospital, Antioxidant and Gene Regulation Laboratory, University of Georgia, 501 D.W. Brooks Drive, Athens, Georgia 30602, USA

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Jianping Ye Department of Physiology and Pharmacology, Renmin Hospital, Antioxidant and Gene Regulation Laboratory, University of Georgia, 501 D.W. Brooks Drive, Athens, Georgia 30602, USA

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Shi-You Chen Department of Physiology and Pharmacology, Renmin Hospital, Antioxidant and Gene Regulation Laboratory, University of Georgia, 501 D.W. Brooks Drive, Athens, Georgia 30602, USA
Department of Physiology and Pharmacology, Renmin Hospital, Antioxidant and Gene Regulation Laboratory, University of Georgia, 501 D.W. Brooks Drive, Athens, Georgia 30602, USA

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, and metabolic energy balance ( Chatterjee et al . 2014 ). Although the underlying mechanism is not fully understood, adipose tissue inflammation has been acknowledged as a critical link between obesity and insulin resistance and type 2 diabetes, and

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Yujiao Dai School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, China

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Peng Hao School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, China

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Zhimei Sun School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, China

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Zhiyi Guo School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China

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Hong Xu School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China

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Lihui Xue Department of Pharmacy, North China University of Science and Technology, Tangshan, Hebei, China

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Hongyu Song Department of Pharmacy, North China University of Science and Technology, Tangshan, Hebei, China

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Yida Li Department of Pharmacy, North China University of Science and Technology, Tangshan, Hebei, China

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Shuang Li Department of Pharmacy, North China University of Science and Technology, Tangshan, Hebei, China

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Mingming Gao School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, China

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Teng Si School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, China

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Yuxin Zhang School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, China
Hebei Key Laboratory for Chronic Diseases, North China University of Science and Technology, Tangshan, Hebei, China
Tangshan Key Laboratory of Basic Research in Medicine Development, North China University of Science and Technology, Tangshan, Hebei, China

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Yajuan Qi School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, China
Hebei Key Laboratory for Chronic Diseases, North China University of Science and Technology, Tangshan, Hebei, China
Tangshan Key Laboratory of Basic Research in Medicine Development, North China University of Science and Technology, Tangshan, Hebei, China

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reverse its progression. However, if Yap is involved in liver fibrosis induced by insulin resistance (IR) has not been reported. In this study, mouse liver fibrosis was induced by IR using HFD stimulation, and the liver YAP pathway and insulin pathway

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Gary J Remington Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8
Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8
Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8

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Celine Teo Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8

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Virginia Wilson Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8

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Araba Chintoh Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8
Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8

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Melanie Guenette Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8

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Zohra Ahsan Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8

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Adria Giacca Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8
Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8

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Margaret K Hahn Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8
Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8
Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, Department of Physiology, 250 College Street, Toronto, Ontario, Canada M5T 1R8

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point, to our knowledge, only two clinical studies exist specifically evaluating insulin resistance or impaired glucose tolerance respectively in the context of antipsychotic treatment ( Henderson et al . 2009 , Smith et al . 2013 ). Both examined

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