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Johanna L Barclay School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia

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Hadiya Agada School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia

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Christina Jang School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia

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Micheal Ward School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia

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Neil Wetzig School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia

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Ken K Y Ho School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia

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). The effect of GCs on BAT in humans is unknown. We have investigated the effects of GCs in a model of primary human adipocytes derived from biopsies of supraclavicular brown adipocyte (BA) depots ( Lee et al . 2011 ). The brown preadipocytes

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Sujith Rajan Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Kripa Shankar Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Muheeb Beg Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Salil Varshney Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Abhishek Gupta Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Ankita Srivastava Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Durgesh Kumar Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Raj K Mishra SIPS Superspeciality Hospital, Lucknow, Uttar Pradesh, India

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Zakir Hussain Division of Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Jiaur R Gayen Division of Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Anil N Gaikwad Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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. In this study for the first time, we have shown the effects of hyperinsulinemia on differentiated and characterized brown adipocytes. Basal chronic hyperinsulinemia (500pM insulin exposure for 72h) causes insulin resistance in both white and brown

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Johannes Klein
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Sören Westphal
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Daniel Kraus
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Britta Meier
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Nina Perwitz
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Volker Ott
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Mathias Fasshauer
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H Harald Klein
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other forms of treatment ( Yki-Jarvinen et al. 1999 ). The adipocyte-derived hormone, leptin, is an essential player in regulating energy homeostasis ( Friedman & Halaas 1998 , Spiegelman & Flier 2001 , Friedman 2002 ). Brown adipose tissue

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Daiana Araujo Santana-Oliveira Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Center, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil

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Henrique Souza-Tavares Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Center, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil

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Aline Fernandes-da-Silva Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Center, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil

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Flavia Maria Silva-Veiga Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Center, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil

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Gustavo Casimiro-Lopes Department of Gymnastics, Physical Education and Sports Institute, Laboratory of Exercise Pathophysiology (LAFE), Rio de Janeiro State University, Rio de Janeiro, Brazil

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Patricia Cristina Lisboa Laboratory of Endocrine Physiology, Biology Institute, Rio de Janeiro State University, Rio de Janeiro, Rio de Janeiro, Brazil

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Carlos Alberto Mandarim-de-Lacerda Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Center, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil

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Vanessa Souza-Mello Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Center, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil

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Introduction Brown adipose tissue (BAT) is a target to fight obesity since nonshivering thermogenesis (NST) occurs exclusively in brown/beige adipocytes and increases energy expenditure by releasing energy as heat ( Wu et al. 2013 ). In

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D Kraus
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M Fasshauer
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V Ott
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B Meier
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M Jost
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HH Klein
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J Klein
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Leptin is an important adipocytokine whose main regulative effects on energy metabolism are exerted via activation of signalling pathways in the central nervous system. Another important regulator of energy homeostasis is insulin. The role of direct autocrine leptin effects on adipose tissue and crosstalk with insulin, in particular in the thermogenically active brown adipose tissue, remains unclear. In the present study, we have investigated leptin secretion and interaction with insulin in highly insulin-responsive immortalised mouse brown adipocytes. Leptin was secreted in a differentiation-dependent manner, and acute leptin treatment of mature adipocytes dose- and time-dependently stimulated phosphorylation of STAT3 and MAP kinase. Interestingly, acute pretreatment of fully differentiated brown adipocytes with leptin (100 nM) significantly diminished insulin-induced glucose uptake by approximately 25%. This inhibitory effect was time-dependent and maximal after 60 min of leptin prestimulation. Furthermore, it correlated with a 35% reduction in insulin-stimulated insulin receptor kinase activity after acute leptin pretreatment. Insulin-induced insulin receptor substrate-1 tyrosine phosphorylation and binding to the regulatory subunit p85 of phosphatidylinositol 3-kinase (PI 3-kinase) were diminished by approximately 60% and 40%, respectively. Taken together, this study has demonstrated strong differentiation-dependent leptin secretion in brown adipocytes and PI 3-kinase-mediated negative autocrine effects of this hormone on insulin action. Direct peripheral leptin-insulin crosstalk may play an important role in the regulation of energy homeostasis.

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V Ott
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M Fasshauer
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A Dalski
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HH Klein
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J Klein
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Ciliary neurotrophic factor (CNTF) plays an important role in regulating neuronal growth. Recently, central anorexigenic effects of this cytokine have been characterized. However, peripheral effects on tissues that actively contribute to the regulation of energy homeostasis have not been described. Here, we report direct potent and selective effects of CNTF on growth factor and metabolic signalling intermediates in mouse brown adipocytes. CNTF stimulates STAT3, MAP kinase, Akt, and p70 S6 kinase. We find that, next to mediating Akt and p70 S6 kinase activation, both phosphatidylinositol 3-kinase and protein kinase C are separately acting, main intermediates for inducing mitogen-activated protein (MAP) kinase activation. On a functional level, CNTF enhances beta3-adrenergic induction of uncoupling protein-1. Thus, these results demonstrate direct effects of CNTF on adipose tissue signalling and metabolism and suggest a novel role for this cytokine in the peripheral regulation of energy homeostasis.

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Garam Yang Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Buk-Gu, Gwangju, Republic of Korea

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Eunjeong Hong Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Buk-Gu, Gwangju, Republic of Korea

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Sejong Oh Division of Animal Science, College of Agriculture & Life Sciences, Chonnam National University, Buk-Gu, Gwangju, Republic of Korea

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Eungseok Kim Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Buk-Gu, Gwangju, Republic of Korea

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inguinal subcutaneous WAT (iWAT) can be converted to brown-like adipocytes, called beige adipocytes. Beige adipocytes highly express uncoupling protein 1 (UCP1), which causes proton leakage from the intermembrane compartment of the mitochondria to acquire

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Joan Villarroya Departament de Bioquímica i Biomedicina Molecular and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Catalonia, Spain
CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain

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Rubén Cereijo Departament de Bioquímica i Biomedicina Molecular and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Catalonia, Spain
CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain

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Aleix Gavaldà-Navarro Departament de Bioquímica i Biomedicina Molecular and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Catalonia, Spain
CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain

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Marion Peyrou Departament de Bioquímica i Biomedicina Molecular and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Catalonia, Spain
CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain

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Marta Giralt Departament de Bioquímica i Biomedicina Molecular and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Catalonia, Spain
CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain

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Francesc Villarroya Departament de Bioquímica i Biomedicina Molecular and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Catalonia, Spain
CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain

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needed; similarly, BAT has been considered to essentially play a role in energy expenditure to support non-shivering thermogenesis. We know that, in brown adipocytes, there is a regulated uncoupling of the mitochondrial respiratory chain relative to ATP

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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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contrast to skeletal muscle cells, BAT progenitors initiate the expression of PRDM16 and BMP7 during development, which drives them to become mature brown adipocytes ( Seale et al . 2008 , Tseng et al . 2008 , Rajakumari et al . 2013 ). The most

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Carsten T Herz Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria

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Florian W Kiefer Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria

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Adipose tissue browning and whitening A hallmark feature of adipose tissue browning is the induction of thermogenically active adipocytes in white fat depots. These adipocytes are often referred to as beige or brite (brown in white) cells and

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