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Marc Schneeberger Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain

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Ramon Gomis Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain

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Marc Claret Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain

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energy balance through behavioral, autonomic, and endocrine outputs. These sophisticated biological programs are influenced by multiple factors, including environmental, genetic, and epigenetic mechanisms. The immense complexity of these systems

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Ruben Nogueiras Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK

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Sulay Tovar Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK

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Sharon E Mitchell Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK

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Perry Barrett Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK

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D Vernon Rayner Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK

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Carlos Dieguez Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK

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Lynda M Williams Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK

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hypothalamus ( Graham et al. 2003 ). These nuclei are important in controlling circadian rhythms, appetite and energy balance ( Takahashi & Zatz 1982 , Williams et al. 2001 ). In contrast, NMU expression in the rat is limited to the SCN, relatively few

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Pryscila D S Teixeira Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil

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Angela M Ramos-Lobo Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil

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Mariana Rosolen Tavares Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil

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Frederick Wasinski Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil

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Renata Frazao Departamento de Anatomia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil

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Jose Donato Jr Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil

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intake and expenditure ( Ramos-Lobo & Donato 2017 ). Thus, genetic mutations that cause the absence of leptin or the leptin receptor (LepR) produce metabolic changes that resemble those observed during intense negative energy balance, including hunger and

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Sharon E Mitchell Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain

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Ruben Nogueiras Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain

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Kellie Rance Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain

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D Vernon Rayner Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain

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Sharon Wood Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain

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Carlos Dieguez Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain

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Lynda M Williams Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain

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Introduction Studies of rodents with either single gene mutations or gene knockouts have led to the discovery of a number of key components of the hypothalamic appetite and energy balance control system ( Williams et al. 2001

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Shin-ya Ueda Department of Sports Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

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Takahiro Yoshikawa Department of Sports Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

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Yoshihiro Katsura Department of Sports Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

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Tatsuya Usui Department of Sports Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

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Hayato Nakao Department of Sports Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

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Shigeo Fujimoto Department of Sports Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

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variations in appetite and post-exercise energy intake (EI), leading to negative energy balance (EB; Blundell & King 1998 , Hubert et al . 1998 ). Recently, there has been growing concern that appetite and energy homeostasis are controlled by a variety of

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K Scrimgeour
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M J Gresham
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L R Giles Faculty of Veterinary Science, Department of Primary Industries, University of Sydney, Camden, New South Wales 2570, Australia

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P C Thomson
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P C Wynn
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R E Newman
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remaining one-third from the small intestine ( Peeters 2005 ). Ghrelin has been shown to have numerous physiological functions that affect energy balance ( Horvath et al . 2001 , Govoni et al . 2005 ), gastrointestinal motility and secretion ( Masuda et

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Christian Doyon Chaire de recherche Merck Frosst/IRSC sur l’obésité and Centre de recherche de l’Hôpital Laval, Hôpital Laval, 2725 chemin Sainte-Foy, Québec, Canada G1V 4G5

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Pierre Samson Chaire de recherche Merck Frosst/IRSC sur l’obésité and Centre de recherche de l’Hôpital Laval, Hôpital Laval, 2725 chemin Sainte-Foy, Québec, Canada G1V 4G5

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Josée Lalonde Chaire de recherche Merck Frosst/IRSC sur l’obésité and Centre de recherche de l’Hôpital Laval, Hôpital Laval, 2725 chemin Sainte-Foy, Québec, Canada G1V 4G5

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Denis Richard Chaire de recherche Merck Frosst/IRSC sur l’obésité and Centre de recherche de l’Hôpital Laval, Hôpital Laval, 2725 chemin Sainte-Foy, Québec, Canada G1V 4G5

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of the CRF 1 receptor in the regulation of energy balance, these antagonists may also prove useful in the pharmacological treatment of obesity, especially in cases where obesity is associated with hyperactivity of the stress axis. Animal

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AR Assali
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A Ganor
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Y Beigel
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Z Shafer
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T Hershcovici
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M Fainaru
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Weight reduction is recommended for the treatment of subjects with insulin resistance (IR) syndrome; however, the relative importance of the decrease in body fat or the negative energy balance achieved during a hypo-energetic diet in the improvement of this metabolic syndrome is still debated. Therefore, we undertook to study their relative impact on amelioration of the metabolic abnormalities associated with IR in obese subjects. Twelve obese subjects (six males and six females, mean+/-s.d. body mass index 36.1+/-4.7 kg/m(2)) aged 38-57 years were investigated. During the first phase they were fed a hypo-energetic diet for 6 weeks (week 0-6). During the second phase, lasting 4 weeks (week 6-10) they consumed an iso-energetic diet. During the third phase (week 10-16) the subjects were put again on a hypo-energetic diet. Insulin sensitivity (SI) was assessed by an insulin-enhanced, frequently sampled i.v. glucose tolerance test with minimal model analysis. All subjects reduced weight during both hypo-energetic periods: 5.49+/-0.75 and 2.32+/-0.37%, means+/-s.e.m., P<0.005, week 0-6 and 10-16 respectively. One-third of this loss was achieved within the first week of each period. SI increased by 353+/-121 and 147+/-38% (P<0.005), means+/-s.e.m., at the end of both hypo-energetic periods (week 6 vs 0 and 16 vs 10 respectively). Two-thirds of this improvement were observed within the first week of each period (week 1 vs 0 and 11 vs 10 respectively). During the iso-energetic weight-maintaining period (week 10 vs 6), SI decreased by 43.5+/-7.9% (P<0.002). Serum levels of leptin and triglyceride followed a similar pattern, but to a lesser extent. It may be concluded that negative energy balance is more effective when compared with maintaining a stable lower weight in achieving an improvement in the metabolic parameters of the IR syndrome.

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Victoria Diedrich Institute of Neurobiology, Ulm University, Ulm, Germany

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Elena Haugg Institute of Neurobiology, Ulm University, Ulm, Germany

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Carola Dreier Institute of Neurobiology, Ulm University, Ulm, Germany

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Annika Herwig Institute of Neurobiology, Ulm University, Ulm, Germany

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: maintaining energy balance during winter. Studying seasonal adaptations of mammals is fascinating because they are very extreme, tightly regulated but also fully reversible. Understanding the underlying regulatory mechanisms will largely contribute to our

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Edra London Section on Endocrinology and Genetics WEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

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Michelle Bloyd Section on Endocrinology and Genetics WEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

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Constantine A Stratakis Section on Endocrinology and Genetics WEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

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1992 , Kim et al. 2018 ). Rare monogenic forms of obesity have facilitated much of our understanding about key molecular pathways involved in maintaining energy balance. Most of these regulatory pathways involve cyclic AMP (cAMP) signaling. The

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