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George Bikopoulos
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Aurelio da Silva Pimenta Department of Laboratory Medicine and Pathobiology, School of Kinesiology and Health Science, Department of Physiology, Clinical Islet Transplant Program, Department of Agricultural, 1 King's College Circle, University of Toronto, Toronto, Canada M5S 1A8

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Simon C Lee Department of Laboratory Medicine and Pathobiology, School of Kinesiology and Health Science, Department of Physiology, Clinical Islet Transplant Program, Department of Agricultural, 1 King's College Circle, University of Toronto, Toronto, Canada M5S 1A8

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Jonathan R Lakey Department of Laboratory Medicine and Pathobiology, School of Kinesiology and Health Science, Department of Physiology, Clinical Islet Transplant Program, Department of Agricultural, 1 King's College Circle, University of Toronto, Toronto, Canada M5S 1A8

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Sandy D Der
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Catherine B Chan Department of Laboratory Medicine and Pathobiology, School of Kinesiology and Health Science, Department of Physiology, Clinical Islet Transplant Program, Department of Agricultural, 1 King's College Circle, University of Toronto, Toronto, Canada M5S 1A8

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Rolando Bacis Ceddia Department of Laboratory Medicine and Pathobiology, School of Kinesiology and Health Science, Department of Physiology, Clinical Islet Transplant Program, Department of Agricultural, 1 King's College Circle, University of Toronto, Toronto, Canada M5S 1A8

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Michael B Wheeler Department of Laboratory Medicine and Pathobiology, School of Kinesiology and Health Science, Department of Physiology, Clinical Islet Transplant Program, Department of Agricultural, 1 King's College Circle, University of Toronto, Toronto, Canada M5S 1A8

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Maria Rozakis-Adcock
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obesity and T2D is characterized as ‘diabesity’ ( Koulouridis 2004 ). A multitude of factors contribute to the pathogenesis of T2D including inflammatory cytokines, increased concentrations of free fatty acids (FFA), adipokines, impaired mitochondrial

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Adrián Plaza Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, Madrid, Spain

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Beatriz Merino Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, Madrid, Spain

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Victoria Cano Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, Madrid, Spain

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Gema Domínguez Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, Madrid, Spain

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Javier Pérez-Castells Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, Madrid, Spain

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M Soledad Fernández-Alfonso Departamento de Farmacología, Instituto Pluridisciplinar, Universidad Complutense, Madrid, Spain

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Coralie Sengenès STROMALab, Université de Toulouse, CNRS ERL5311, EFS, INP-ENVT, Inserm U1031, UPS, Toulouse, France

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Julie A Chowen Departamento de Endocrinología, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria Princesa, CIBEROBN Instituto Carlos III, Madrid, Spain

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Mariano Ruiz-Gayo Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, Madrid, Spain

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intake; (ii) delaying gastric emptying; (iii) facilitating intestinal digestion of fat and TG absorption and (iv) enhancing fatty acid (FA) catabolism in oxidative tissues. More recently, King and coworkers demonstrated that FA uptake by adipose tissue in

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Ricardo Rodríguez-Calvo Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, ‘Sant Joan’ University Hospital, Universitat Rovira i Virgili, Institut de Investigació Sanitaria Pere Virgili (IISPV), Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain

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Josefa Girona Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, ‘Sant Joan’ University Hospital, Universitat Rovira i Virgili, Institut de Investigació Sanitaria Pere Virgili (IISPV), Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain

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Josep M Alegret Department of Cardiology, Cardiovascular Research Group, ‘Sant Joan’ University Hospital, Universitat Rovira i Virgili, Institut de Investigació Sanitaria Pere Virgili (IISPV), Reus, Spain

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Alba Bosquet Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, ‘Sant Joan’ University Hospital, Universitat Rovira i Virgili, Institut de Investigació Sanitaria Pere Virgili (IISPV), Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain

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Daiana Ibarretxe Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, ‘Sant Joan’ University Hospital, Universitat Rovira i Virgili, Institut de Investigació Sanitaria Pere Virgili (IISPV), Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain

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Lluís Masana Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, ‘Sant Joan’ University Hospital, Universitat Rovira i Virgili, Institut de Investigació Sanitaria Pere Virgili (IISPV), Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain

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. 2013 , Liu et al . 2013 ). Among these adipokines, fatty acid-binding protein 4 (FABP4) has recently been linked to cardiovascular and metabolic diseases. Additionally, FABP4 is highly expressed in macrophages, contributing to the development of

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D C Ferguson Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA

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Z Caffall Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA

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M Hoenig Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA

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multi-species leptin ELISA as validated for cats ( Hoenig et al. 2003 ). Nonesterified fatty acids (NEFAs) were measured using an enzymatic test kit (Wako Diagnostic, Richmond, PA, USA). In the cats, the FT 4 fraction expressed as a percentage was

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Alia H Sukkar Section for Nutrition Research, Department of Medicine, Imperial College London, London, UK

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Aaron M Lett Section for Nutrition Research, Department of Medicine, Imperial College London, London, UK

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Gary Frost Section for Nutrition Research, Department of Medicine, Imperial College London, London, UK

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Edward S Chambers Section for Nutrition Research, Department of Medicine, Imperial College London, London, UK

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our total body weight ( Almeida et al. 2019 ). Short-chain fatty acids (SCFAs) are the major metabolic end products of gut microbial fermentation of dietary fibre with acetate, propionate and butyrate, generated in an approximate molar ratio of 60

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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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Sandra Pereira Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Wen Qin Yu Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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María E Frigolet Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Jacqueline L Beaudry Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Yaniv Shpilberg Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Edward Park Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Cristina Dirlea Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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B L Grégoire Nyomba Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Michael C Riddell Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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I George Fantus Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Adria Giacca Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Introduction Obesity leads to type 2 diabetes mellitus (T2DM) because of insulin resistance, and insulin resistance of obesity is due to elevated circulating levels of free fatty acids (FFAs) and cytokines ( Boden 1997 , Lewis et al . 2002

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Eleftheria Diakogiannaki Peninsula Medical School, Institute of Biomedical and Clinical Science, John Bull Building, Plymouth PL6 8BU, UK

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Hannah J Welters Peninsula Medical School, Institute of Biomedical and Clinical Science, John Bull Building, Plymouth PL6 8BU, UK

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Noel G Morgan Peninsula Medical School, Institute of Biomedical and Clinical Science, John Bull Building, Plymouth PL6 8BU, UK

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development of type 2 diabetes. In particular, it has been proposed that the hyperlipidaemia which can accompany obesity may lead to an elevation in plasma levels of free fatty acids ( Gordon 1960 , Unger 1995 , Sabin et al . 2007 ) which, in turn

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Edward Park
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Victor Wong
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Xinyu Guan
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Andrei I Oprescu
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Adria Giacca
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free fatty acids (FFAs), from the expanded adipose tissue in obese individuals. In particular, elevated circulating levels of FFA cause insulin resistance in both animals and humans ( Roden et al . 1996 , Boden et al . 2001 , Yuan et al . 2001

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Fátima Pérez de Heredia Department of Physiology, University of Murcia, Murcia, 30100 Spain

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Elvira Larqué Department of Physiology, University of Murcia, Murcia, 30100 Spain

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Salvador Zamora Department of Physiology, University of Murcia, Murcia, 30100 Spain

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Marta Garaulet Department of Physiology, University of Murcia, Murcia, 30100 Spain

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, Sánchez et al . 2008 ). In addition, DHEA-S can modulate fatty acid (FA) metabolism, through up-regulation of hepatic enzymes involved in β-oxidation ( Waxman 1996 , Depreter et al . 2002 ). The relevance of FAs is far beyond their role as energy

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