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Alvaro Souto Padron Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Ruy Andrade Louzada Neto Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil
Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Thiago Urgal Pantaleão Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Maria Carolina de Souza dos Santos Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Renata Lopes Araujo Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Bruno Moulin de Andrade Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Monique da Silva Leandro Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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João Pedro Saar Werneck de Castro Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Andrea Claudia Freitas Ferreira Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Denise Pires de Carvalho Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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administered to control animals ( Lanni et al . 2005 ). Additionally, Lombardi et al . (2009) demonstrated that 3,5-T2 rapidly enhances the fatty acid oxidation rate in skeletal muscle. Apart from the chronic effects of 3,5-T2, acute and most likely non

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Sushil K Mahata VA San Diego Healthcare System Metabolic Physiology & Ultrastructural Biology Lab., Department of Medicine, University of California at San Diego, La Jolla, CA, USA

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Hong Zheng Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA

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Sumana Mahata Caltech Division of Biology, California Institute of Technology, Pasadena, CA, USA

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Xuefei Liu Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA

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Kaushik P Patel Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA

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-activated receptor-γ (PPARγ) coactivator 1α (PGC-1α) is a major regulator of exercise-induced phenotypic adaptation and substrate utilization. A modest (~25%) upregulation of PGC-1α improves mitochondrial biogenesis and fatty acid oxidation in healthy and insulin

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K L Davies Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

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E J Camm Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Australia

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D J Smith Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

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O R Vaughan Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
Institute for Women’s Health, University College London, London, UK

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A J Forhead Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK

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A J Murray Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

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A L Fowden Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

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of fatty acid oxidation capacity. In all protocols, leak state was measured in the presence of substrates before the addition of ADP, and the experiment concluded with the addition of cytochrome c (10 µM) to check outer mitochondrial membrane

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Taira Wada Laboratory of Health Science, School of Pharmacy, Nihon University, Funabshi, Chiba, Japan

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Yukiko Yamamoto Laboratory of Health Science, School of Pharmacy, Nihon University, Funabshi, Chiba, Japan

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Yukiko Takasugi Laboratory of Health Science, School of Pharmacy, Nihon University, Funabshi, Chiba, Japan

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Hirotake Ishii Laboratory of Health Science, School of Pharmacy, Nihon University, Funabshi, Chiba, Japan

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Taketo Uchiyama Laboratory of Organic Chemistry, School of Pharmacy, Nihon University, Funabshi, Chiba, Japan

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Kaori Saitoh Department of Psychiatry, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan

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Masahiro Suzuki Department of Psychiatry, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan

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Makoto Uchiyama Department of Psychiatry, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
Tokyo Adachi Hospital, Adachi, Tokyo, Japan

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Hikari Yoshitane Department of Biological Sciences, School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

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Yoshitaka Fukada Department of Biological Sciences, School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

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Shigeki Shimba Laboratory of Health Science, School of Pharmacy, Nihon University, Funabshi, Chiba, Japan

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, total cholesterol, HDL cholesterol, LDL cholesterol, non-esterified fatty acids (NEFA) (FUJIFILM Wako Pure Chemical Co. ltd., Osaka, Japan), insulin (Morinaga Institute of Biological Science, Inc., Kanagawa, Japan), and adiponectin (Otsuka Pharmaceutical

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R Prasad Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK

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J C Kowalczyk Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK

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E Meimaridou Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK

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H L Storr Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK

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L A Metherell Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK

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distribution and retention of selenium in the rat . Journal of Nutrition 114 1289 – 1296 . Brites P Mooyer PA El Mrabet L Waterham HR Wanders RJ 2009 Plasmalogens participate in very-long-chain fatty acid-induced pathology . Brain 132

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Gisela Helfer School of Chemistry and Biosciences, University of Bradford, Bradford, UK

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Qing-Feng Wu State Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China

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). Diabetes Recently, novel adipokines such as vaspin, omentin, retinal-binding protein-4, fibroblast growth factor 21, adipocyte fatty acid-binding protein and dipeptidyl peptidase 4 were found to associate with insulin resistance and T2DB in humans

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T V Novoselova Centre for Endocrinology, Queen Mary University of London, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London, UK

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R Larder University of Cambridge Metabolic Research Laboratories, MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UK

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D Rimmington University of Cambridge Metabolic Research Laboratories, MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UK

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C Lelliott Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

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E H Wynn Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

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R J Gorrigan Centre for Endocrinology, Queen Mary University of London, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London, UK

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P H Tate Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

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L Guasti Centre for Endocrinology, Queen Mary University of London, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London, UK

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The Sanger Mouse Genetics Project Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

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S O’Rahilly University of Cambridge Metabolic Research Laboratories, MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UK

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A J L Clark Centre for Endocrinology, Queen Mary University of London, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London, UK

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D W Logan Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

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A P Coll University of Cambridge Metabolic Research Laboratories, MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UK

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L F Chan Centre for Endocrinology, Queen Mary University of London, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London, UK

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at 22°C followed by incubation at 4°C overnight with the primary antibody: anti-ACTB antibody 1/10,000 (Abcam), anti-UCP1 1/5000 (Abcam) and antibodies for Fatty Acid and Lipid Metabolism and Lipolysis Activation (8334, 8335 Cell Signaling Technology

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Alessandro Pocai Diabetes and Endocrinology, Merck Research Laboratories, Merck Sharp and Dohme Corp., 126 East Lincoln Avenue, Rahway, New Jersey 07065, USA

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increases thermogenesis, satiety, lipolysis, fatty acid oxidation, and ketogenesis ( Salter 1960 , Salter et al . 1960 , Penick & Hinkle 1961 , Langhans et al . 1982 , Habegger et al . 2010 , Jones et al . 2012 ). A critical physiological role of

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Gulizar Issa Ameen Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK

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Silvia Mora Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK

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utilization and fatty acid activating AMP-activated protein kinase. Nature Medicine 8 1288 – 1295 . ( https://doi.org/10.1038/nm788 ) 12368907 10.1038/nm788 Yang C Mora S Ryder JW Coker KJ Hansen P Allen LA Pessin JE 2001

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Elisa Villalobos University/British Heart Foundation Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom

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Allende Miguelez-Crespo University/British Heart Foundation Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom

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Ruth A Morgan University/British Heart Foundation Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
Scotland’s Rural College, The Roslin Institute, Easter Bush Campus, United Kingdom

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Lisa Ivatt University/British Heart Foundation Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom

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Mhairi Paul University/British Heart Foundation Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom

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Joanna P Simpson University/British Heart Foundation Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom

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Natalie Z M Homer University/British Heart Foundation Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom

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Dominic Kurian The Roslin Institute, Royal (Dick) School of Veterinary Studies, College of Medicine and Veterinary Medicine, University of Edinburgh, Easter Bush Campus, Edinburgh, United Kingdom

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Judit Aguilar The Roslin Institute, Royal (Dick) School of Veterinary Studies, College of Medicine and Veterinary Medicine, University of Edinburgh, Easter Bush Campus, Edinburgh, United Kingdom

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Rachel A Kline The Roslin Institute, Royal (Dick) School of Veterinary Studies, College of Medicine and Veterinary Medicine, University of Edinburgh, Easter Bush Campus, Edinburgh, United Kingdom

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Thomas M Wishart The Roslin Institute, Royal (Dick) School of Veterinary Studies, College of Medicine and Veterinary Medicine, University of Edinburgh, Easter Bush Campus, Edinburgh, United Kingdom

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Nicholas M Morton University/British Heart Foundation Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
Centre for Systems Health and Integrated Metabolic Research, Nottingham Trent University, Nottingham, United Kingdom

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Roland H Stimson University/British Heart Foundation Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom

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Ruth Andrew University/British Heart Foundation Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom

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Brian R Walker University/British Heart Foundation Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom

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Mark Nixon University/British Heart Foundation Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom

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TissueLyser II (Qiagen) and 5 mm stainless-steel beads (30 Hz, three cycles of 15 s). Protein concentration was quantified using a bicinchoninic acid (BCA) assay (Thermo Scientific). Extracted proteins (25 µg) were resolved by SDS-PAGE, using Criterion TGX

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