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T’ng Choong Kwok University/BHF Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, United Kingdom

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

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fatty acids, which subsequently activate a specialised thermogenic protein known as uncoupling protein 1 (UCP1) ( Cannon & Nedergaard 2004 ). UCP1 is located on the inner mitochondrial membrane and generates heat by uncoupling oxidative phosphorylation

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Hyo Youl Moon
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Parkyong Song BioSignal Network Laboratory, Division of Molecular and Life Sciences, Lee Gil Ya Cancer and Diabetes Institute, School of Nano-Biotechnology and Chemical Engineering, Ulsan National Institute of Science and Technology, Engineering Building 104, 689-805 Ulsan, Republic of Korea

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Cheol Soo Choi BioSignal Network Laboratory, Division of Molecular and Life Sciences, Lee Gil Ya Cancer and Diabetes Institute, School of Nano-Biotechnology and Chemical Engineering, Ulsan National Institute of Science and Technology, Engineering Building 104, 689-805 Ulsan, Republic of Korea

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Sung Ho Ryu BioSignal Network Laboratory, Division of Molecular and Life Sciences, Lee Gil Ya Cancer and Diabetes Institute, School of Nano-Biotechnology and Chemical Engineering, Ulsan National Institute of Science and Technology, Engineering Building 104, 689-805 Ulsan, Republic of Korea

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Pann-Ghill Suh
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precise mechanism of hepatic lipid accumulation remains incompletely understood, abnormal regulation of lipid disposal through fatty acid (FA) oxidation and processes affecting lipid availability, such as circulating free FA (FFA) uptake, have been

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M E Cleasby Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK
Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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Q Lau Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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E Polkinghorne Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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S A Patel Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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S J Leslie Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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N Turner Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK
Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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G J Cooney Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK
Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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A Xu Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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E W Kraegen Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK
Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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adiponectin to increase both fatty acid oxidation and glucose disposal into skeletal muscle ( Yamauchi et al . 2002 , Yoon et al . 2006 ) and additionally to improve insulin sensitivity ( Yamauchi et al . 2001 ) has been proposed, effects that have been

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Jethro S Johnson Computational Genomics Analysis and Training, Medical Research Council-Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK

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Monica N Opiyo University/BHF Centre for Cardiovascular Science, Queen’s Medical Research Institute, Edinburgh, UK

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Marian Thomson Edinburgh Genomics, Ashworth Laboratories, University of Edinburgh, Edinburgh, UK

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Karim Gharbi Edinburgh Genomics, Ashworth Laboratories, University of Edinburgh, Edinburgh, UK

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Jonathan R Seckl University/BHF Centre for Cardiovascular Science, Queen’s Medical Research Institute, Edinburgh, UK

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Andreas Heger Computational Genomics Analysis and Training, Medical Research Council-Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK

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Karen E Chapman University/BHF Centre for Cardiovascular Science, Queen’s Medical Research Institute, Edinburgh, UK

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Morgan SA Rose AJ Herzig S Lavery GG Odermatt A 2014 11β-Hydroxysteroid dehydrogenase-1 is involved in bile acid homeostasis by modulating fatty acid transport protein-5 in the liver of mice . Molecular Metabolism 3 554 – 564

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Joachim M Weitzel Institute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany

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Torsten Viergutz Institute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany

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Dirk Albrecht Institute of Microbiology, Ernst-Moritz-Arndt-University, Greifswald, Germany

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Rupert Bruckmaier Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland

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Marion Schmicke Clinic for Cattle, Endocrinology Laboratory, University of Veterinary Medicine Hannover, Hannover, Germany

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Armin Tuchscherer Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany

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Franziska Koch Institute of Nutritional Physiology ‘Oskar Kellner’, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany

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Björn Kuhla Institute of Nutritional Physiology ‘Oskar Kellner’, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany

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abundance of THRA , NRF1 , DIO1 and PPARGC1A was greater than in HS cows, a regulation which might help to switch hepatic metabolism toward fatty acid oxidation during times of energy deficiency at thermoneutrality. A switch of metabolic rate and a

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Nikolaos Nikolaou Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Anastasia Arvaniti Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK

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Nathan Appanna Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Anna Sharp Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Beverly A Hughes Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham, UK

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Dena Digweed Diurnal Ltd, Cardiff, UK

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Martin J Whitaker Diurnal Ltd, Cardiff, UK

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Richard Ross Department of Oncology and Metabolism, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK

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Wiebke Arlt Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham, UK
NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK

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Trevor M Penning Department of Systems Pharmacology & Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA

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Karen Morris Biochemistry Department, Manchester University NHS Trust, Manchester, UK

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Sherly George Biochemistry Department, Manchester University NHS Trust, Manchester, UK

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Brian G Keevil Biochemistry Department, Manchester University NHS Trust, Manchester, UK

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Leanne Hodson Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Laura L Gathercole Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK

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Jeremy W Tomlinson Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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well as increasing functional de novo lipogenesis, as measured by deuterated water incorporation into fatty acids ( Nikolaou et al. 2019 b ). The data from our study now provide additional evidence of the adverse impact of AKR1D1 down

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Mark E Cleasby Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London, UK

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Pauline M Jamieson Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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Philip J Atherton Division of Medical Sciences and Graduate Entry Medicine, University of Nottingham, Medical School, Royal Derby Hospital, Derby, UK

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mediator of ribosomal protein synthesis, in rodent muscle and a saturated fatty acid (SFA)/ceramide-induced increase in elongation factor 2α activation in cultured muscle cells ( Tardif et al. 2014 ). However, the nature of the lipids is important because

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Rui Gao Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK

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Samuel Acreman Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK
Department of Physiology, Institute of Neuroscience and Physiology, Metabolic Research Unit, University of Gothenburg, Göteborg, Sweden

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Jinfang Ma Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK

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Fernando Abdulkader Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil

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Anna Wendt Department of Clinical Sciences Malmö, Islet Cell Exocytosis, Lund University Diabetes Centre, Lund University, Malmö, Sweden

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Quan Zhang Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK
CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal

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can transfer phosphate to ADP to produce ATP, as it does in β-cells ( Krippeit-Drews et al. 2003 ). Moreover, it was proposed that α-cells can generate ATP via fatty acid oxidation ( Briant et al. 2018 ). In mice with α-cells lacking CPT1, an

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Kevin J P Ryan Division of Nutritional Sciences, School of Biosciences, University of Nottingham, Loughborough, Leics LE12 5RD, UK

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Zoe C T R Daniel Division of Nutritional Sciences, School of Biosciences, University of Nottingham, Loughborough, Leics LE12 5RD, UK

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Lucinda J L Craggs Division of Nutritional Sciences, School of Biosciences, University of Nottingham, Loughborough, Leics LE12 5RD, UK

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Tim Parr Division of Nutritional Sciences, School of Biosciences, University of Nottingham, Loughborough, Leics LE12 5RD, UK

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John M Brameld Division of Nutritional Sciences, School of Biosciences, University of Nottingham, Loughborough, Leics LE12 5RD, UK

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all three adipose-specific marker genes, PPAR γ 2 ( PPARG ; Fig. 3 A), fatty acid binding protein 4 ( FABP4 ; Fig. 3 B) and adiponectin/ ADIPOQ ( Fig. 3 C), were induced in a 1,25(OH) 2 D 3 concentration and time-dependent manner ( P <0.001 for

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Erica Yeo Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada

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Patricia L Brubaker Department of Physiology, University of Toronto, Toronto, ON, Canada
Department of Medicine, University of Toronto, Toronto, ON, Canada

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Deborah M Sloboda Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
Department of Obstetrics, Gynecology and Pediatrics, McMaster University, Hamilton, ON, Canada

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. 2 ), including the fermentation of non-digestible carbohydrates into short-chain fatty acids (SCFA), the processing of bile acids (BA) into secondary BAs, and the unique processing of amino acids such as tryptophan into indole compounds. The most

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