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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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balance where daily energy intake exceeds energy expenditure ( Hill & Peters 1998 , Caballero 2007 ). Based on the average weight gain observed in early- and middle-aged adults (~0.5 kg/year) ( Williamson et al. 1990 , Hebden et al. 2012 ), it is

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Hiroyuki Shimizu Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan
Department of Regulation Biology, Saitama University, Saitama 378-8570, Japan

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Kinji Inoue Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan
Department of Regulation Biology, Saitama University, Saitama 378-8570, Japan

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Masatomo Mori Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan
Department of Regulation Biology, Saitama University, Saitama 378-8570, Japan

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decreased energy expenditure lead to obesity ( Spiegelman & Flier 2001 ) and both are regulated essentially by the hypothalamus. The hypothalamus is a known center for the regulation of fundamental behaviors including appetite, thirst, temperature, sexual

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Rumana Yasmeen Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA

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Qiwen Shen Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA

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Aejin Lee Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA

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Jacob H Leung Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA

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Devan Kowdley Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA

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David J DiSilvestro Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA

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Lu Xu Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA
Department of Minimally Invasive Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

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Kefeng Yang Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA
Department of Nutrition, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

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Andrei Maiseyeu Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

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Naresh C Bal Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA
KIIT School of Biotechnology, KIIT University, Bhubaneswar, India

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Muthu Periasamy Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA

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Paolo Fadda Nucleic Acid Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA

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Ouliana Ziouzenkova Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA

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receptor (LepR) belonging to the interleukin 6 (IL-6) type family of cytokine receptors ( Peelman et al . 2014 ). LEP regulation of energy expenditure, lipolysis, basal and cold induced thermogenesis, as well as satiety, is attributed to its neuroendocrine

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Nigel Turner Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia
Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia

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Gregory J Cooney Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia
Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia

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Edward W Kraegen Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia
Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia

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Clinton R Bruce Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia

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(obesity) and reduced insulin action (insulin resistance) in muscle, this article will deal with FAs as an alternative energy substrate to glucose, the relevance of this substrate competition to overall energy expenditure and an assessment of the various

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Juliane K Czeczor Metabolic Research Unit, School of Medicine and Centre for Molecular and Medical Research, Deakin University, Geelong, Victoria, Australia

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Amanda J Genders Metabolic Research Unit, School of Medicine and Centre for Molecular and Medical Research, Deakin University, Geelong, Victoria, Australia

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Kathryn Aston-Mourney Metabolic Research Unit, School of Medicine and Centre for Molecular and Medical Research, Deakin University, Geelong, Victoria, Australia

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Timothy Connor Metabolic Research Unit, School of Medicine and Centre for Molecular and Medical Research, Deakin University, Geelong, Victoria, Australia

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Liam G Hall Metabolic Research Unit, School of Medicine and Centre for Molecular and Medical Research, Deakin University, Geelong, Victoria, Australia

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Kyoko Hasebe Metabolic Research Unit, School of Medicine and Centre for Molecular and Medical Research, Deakin University, Geelong, Victoria, Australia

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Megan Ellis Metabolic Research Unit, School of Medicine and Centre for Molecular and Medical Research, Deakin University, Geelong, Victoria, Australia

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Kirstie A De Jong Metabolic Research Unit, School of Medicine and Centre for Molecular and Medical Research, Deakin University, Geelong, Victoria, Australia

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Darren C Henstridge Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia

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Peter J Meikle Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia

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Mark A Febbraio Division of Diabetes and Metabolism, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia

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Ken Walder Metabolic Research Unit, School of Medicine and Centre for Molecular and Medical Research, Deakin University, Geelong, Victoria, Australia

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Sean L McGee Metabolic Research Unit, School of Medicine and Centre for Molecular and Medical Research, Deakin University, Geelong, Victoria, Australia
Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia

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neurons, but also in peripheral tissues that contribute to whole body metabolic homeostasis. Non-amyloidogenic processing of APP can positively influence aspects of metabolism. For example, BACE-1-deficient mice have increased energy expenditure that

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Riccardo Dore Department of Internal Medicine I, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany

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Luka Levata Department of Internal Medicine I, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany

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Sogol Gachkar Department of Internal Medicine I, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany

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Olaf Jöhren Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany

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Jens Mittag Department of Internal Medicine I, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany

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Hendrik Lehnert Department of Internal Medicine I, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany

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Carla Schulz Department of Internal Medicine I, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany

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the melanocortin 3/4 receptor (MC3/4R) antagonist SHU9119, indicating the recruitment of the central melanocortin system by nesfatin-1. Similarly, stimulation of central MC4R suppresses food intake and increases energy expenditure ( Fan et al. 1997

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João Paulo G Camporez Department of Internal Medicine, Howard Hughes Medical Institute, Service of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06536, USA

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Mohamed Asrih Department of Internal Medicine, Howard Hughes Medical Institute, Service of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06536, USA

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Dongyan Zhang Department of Internal Medicine, Howard Hughes Medical Institute, Service of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06536, USA
Department of Internal Medicine, Howard Hughes Medical Institute, Service of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06536, USA

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Mario Kahn Department of Internal Medicine, Howard Hughes Medical Institute, Service of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06536, USA
Department of Internal Medicine, Howard Hughes Medical Institute, Service of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06536, USA

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Varman T Samuel Department of Internal Medicine, Howard Hughes Medical Institute, Service of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06536, USA

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Michael J Jurczak Department of Internal Medicine, Howard Hughes Medical Institute, Service of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06536, USA
Department of Internal Medicine, Howard Hughes Medical Institute, Service of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06536, USA

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François R Jornayvaz Department of Internal Medicine, Howard Hughes Medical Institute, Service of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06536, USA
Department of Internal Medicine, Howard Hughes Medical Institute, Service of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06536, USA

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intermediates known to activate protein kinase C epsilon (PKCε), which subsequently impairs insulin signaling ( Samuel et al . 2007 ). Lower body weight in mice fed a KD was secondary to higher energy expenditure, which was attributed to an increase in FGF21

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Qinghua Wang State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China
Laboratory Animal Center, Nantong University, Nantong, Jiangsu, China

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Jing Tang State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China

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Shujun Jiang State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China
School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, Jiangsu, China

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Zan Huang State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China
Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, China

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Anying Song State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China

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Siyuan Hou State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China

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Xiang Gao State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China

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Hai-Bin Ruan Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA

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). Total energy expenditure indicated by calculated heat production was reduced in KO mice during early hours into the dark phase ( Fig. 6C ). Reduced physical activity was also observed in KO mice, particularly during the dark phase ( Fig. 6D ). We then

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Amy Warner AstraZeneca, Center of Brain, CVMD IMED, Pepparedsleden 1, 43183 Mölndal, Sweden

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Jens Mittag AstraZeneca, Center of Brain, CVMD IMED, Pepparedsleden 1, 43183 Mölndal, Sweden

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could be turned to burning fuel instead of storing. This review summarizes the current knowledge on thermogenic adipose tissue and discusses its possible use in elevating energy expenditure to counteract obesity and metabolic diseases such as type 2

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David M Cartwright Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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Lucy A Oakey Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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Rachel S Fletcher Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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Craig L Doig Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
School of Science and Technology, Nottingham Trent University, Nottingham, UK

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Silke Heising Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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Dean P Larner Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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Daniela Nasteska Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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Caitlin E Berry Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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Sam R Heaselgrave Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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Christian Ludwig Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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David J Hodson Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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Gareth G Lavery Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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Antje Garten Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
Pediatric Research Center, Hospital for Child and Adolescent Medicine, Leipzig University, Leipzig, Germany

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’s instructions. One lobe (lobus hepatis sinister) was fixed in 4% paraformaldehyde and paraffin-embedded. Sections were stained with hematoxylin and images were taken at 20× magnification. Indirect calorimetry Energy expenditure, respiratory exchange

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