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Systemic glucocorticoid excess causes several adverse metabolic conditions, most notably Cushing’s syndrome. These effects are amplified by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Here we determined the less well characterised effects of glucocorticoid excess, and the contribution of 11β-HSD1 amplification, on metabolic rate in mice. Male and female C57BL/6J (wild type, WT) and 11β-HSD1 knock out (11β-HSD1KO) mice were treated with high-dose corticosterone or a vehicle control for 3 weeks. Indirect calorimetry was conducted during the final week of treatment, with or without fasting, to determine the impact on metabolic rate. We found that corticosterone treatment elevated metabolic rate and promoted carbohydrate utilisation primarily in female WT mice, with effects more pronounced during the light phase. Corticosterone treatment also resulted in greater fat accumulation in female WT mice. Corticosterone induced hyperphagia was identified as a likely causal factor altering the respiratory exchange ratio (RER) but not energy expenditure (EE). Male and female 11β-HSD1KO mice were protected against these effects. We identify novel metabolic consequences of sustained glucocorticoid excess, identify a key mechanism of hyperphagia and demonstrate that 11β-HSD1 is required to manifest the full metabolic derangement.
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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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Introduction Compound 3,3′,5-triiodothyronine (T 3 ) exerts many important effects on the basal metabolic rate and increases oxygen consumption. Several years ago, it was shown that 3,5-diiodothyronine (3,5-T2) is responsible for certain non
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metabolic rate ( Baskin et al . 1999 , Cone et al . 2001 ). This occurs principally via the action of α-melanocyte-stimulating hormone (α-MSH), a peptide derived from the proopiomelanocortin (POMC)-expressing neurons in the hypothalamus and brainstem
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
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Department of Diabetes, Endocrinology and Nutrition, Hospital de Girona ‘Dr Josep Trueta’, Institut D’investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain
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CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
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CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
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Department of Clinical Science, KG Jebsen Center for Diabetes Research, University of Bergen, Bergen, Norway
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CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
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CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
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Department of Diabetes, Endocrinology and Nutrition, Hospital de Girona ‘Dr Josep Trueta’, Institut D’investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain
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CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
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the metabolic rate and the patients suffering from this condition undergo body weight loss, despite increased food intake; quite the opposite, hypothyroid patients show lowered metabolic rate and reduced food intake ( Brenta et al . 2007 , Kaptein
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MC4-R agonists leads to a suppression of appetite and increases the metabolic rate resulting in a significant weight loss ( Li et al . 2004 ). Furthermore mice, rats, and humans deficient in the MC4-R are obese ( Huszar et al . 1997 , Vaisse et al
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in triiodothyronine and thyroxine concentrations by 40–47% after a 7 -day challenge. This has been expected as essential in order to ensure the demand for a reduced metabolic rate and to confine increase in body temperature in these animals ( McGuire
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metabolic rate are also likely to be much reduced ( Breton et al. 1983 ). In good accord with this, in the current study, the peptidic GCGR antagonists both decreased physical activity in HFF-STZ mice. However, the ability of desHis 1 Pro 4 Glu 9 -glucagon
Department of Diabetes and Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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Department of Diabetes and Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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Centre of Endocrinology Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
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Department of Diabetes and Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Centre of Endocrinology Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
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(shift work, working hours, occupational stress), (17) postmenopausal hormone use, (18) metabolic rate, (19) study or institution level, (20) insulin sensitivity, (21) napping, (22) total calorie intake, (23) dietary habits. HbA1c, haemoglobin A1c
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despite the fact that there is a large body of evidence indicating that differences in metabolic rate can predict changes in weight ( Ravussin et al . 1988 ) and that an increase in peripheral metabolism such as after treatment with thyroid hormone or
German Center for Diabetes Research (DZD), Neuherberg, Germany
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German Center for Diabetes Research (DZD), Neuherberg, Germany
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German Center for Diabetes Research (DZD), Neuherberg, Germany
Division of Metabolic Diseases, Technische Universität, Munich, Germany
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German Center for Diabetes Research (DZD), Neuherberg, Germany
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glycemic control by bariatric surgery is rapid and is often observed even before a clinically relevant weight loss ( Pories et al. 1995 , Peterli et al. 2009 , Bayham et al. 2012 ). Despite intense scientific investigation, changes in metabolic rate