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Åsa Tivesten
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Anna Barlind
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Claes Ohlsson
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Jörgen Isgaard
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. 2000 ), arterial stiffness ( Smith et al. 2002 ), endothelial and/or endothelium-independent vasodilation ( Rossoni et al. 1999 , Evans et al. 2000 , Capaldo et al. 2001 ), and may reverse markers of early atherosclerosis ( Pfeifer et al

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Hongbin Liu Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia
Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia

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Anthony E Dear Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia
Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia

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Lotte B Knudsen Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia

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Richard W Simpson Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia
Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia
Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia

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Introduction Type 2 diabetes is characterized by accelerated atherosclerosis ( Hobb 2006 ). Elevated tumour necrosis factor α (TNF) levels and hyperglycaemia are implicated in diabetes-associated endothelial cell dysfunction and may be causal in

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Yunshan Hu Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran, Melbourne, Victoria, Australia 3181
Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran, Melbourne, Victoria, Australia 3181

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Hong Bin Liu Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran, Melbourne, Victoria, Australia 3181
Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran, Melbourne, Victoria, Australia 3181

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Richard W Simpson Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran, Melbourne, Victoria, Australia 3181
Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran, Melbourne, Victoria, Australia 3181

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Anthony E Dear Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran, Melbourne, Victoria, Australia 3181
Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran, Melbourne, Victoria, Australia 3181

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Introduction Type 2 diabetes is characterised by accelerated atherosclerosis ( Hobb 2006 ). Elevated tumour necrosis factor α (TNFα) levels and hyperglycaemia are implicated in diabetes-associated endothelial cell dysfunction and may be causal in

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Alexia Barroso Department of Cell Biology, Physiology, and Immunology, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia University Hospital, Cordoba, Spain
CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain

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Jose Antonio Santos-Marcos CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain
Lipids and Atherosclerosis Research Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain

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Cecilia Perdices-Lopez Department of Cell Biology, Physiology, and Immunology, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia University Hospital, Cordoba, Spain
CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain

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Ana Vega-Rojas CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain
Lipids and Atherosclerosis Research Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain

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Miguel Angel Sanchez-Garrido Department of Cell Biology, Physiology, and Immunology, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia University Hospital, Cordoba, Spain
CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain

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Yelizabeta Krylova CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain
Lipids and Atherosclerosis Research Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain

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Helena Molina-Abril Department of Applied Mathematics I, University of Seville, Seville, Spain

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Claes Ohlsson Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Pablo Perez-Martinez CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain
Lipids and Atherosclerosis Research Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain

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Matti Poutanen Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland

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Jose Lopez-Miranda CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain
Lipids and Atherosclerosis Research Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain

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Manuel Tena-Sempere Department of Cell Biology, Physiology, and Immunology, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia University Hospital, Cordoba, Spain
CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain
Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland

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Antonio Camargo CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain
Lipids and Atherosclerosis Research Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain

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Gonadal steroids strongly contribute to the metabolic programming that shapes the susceptibility to the manifestation of diseases later in life, and the effect is often sexually dimorphic. Microbiome signatures, together with metabolic traits and sex steroid levels, were analyzed at adulthood in neonatally androgenized female rats, and compared with those of control male and female rats. Exposure of female rats to high doses of androgens on early postnatal life resulted in persistent alterations of the sex steroid profile later on life, namely lower progesterone and higher estradiol and estrone levels, with no effect on endogenous androgens. Neonatally androgenized females were heavier (10% at early adulthood and 26% at adulthood) than controls and had impaired glucose homeostasis observed by higher AUC of glucose in GTT and ITT when subjected to obesogenic manipulations. Androgenized female displayed overt alterations in gut microbiota, indicated especially by higher Bacteroidetes and lower Firmicutes abundance at early adulthood, which disappeared when animals were concurrently overfed at adulthood. Notably, these changes in gut microbiota were related with the intestinal expression of several miRNAs, such as miR-27a-3p, miR-29a-5p, and miR-100-3p. Our results suggest that nutritional and hormonal disruption at early developmental periods not only alters the metabolic programming of the individual later in life but also perturbs the architecture of gut microbiota, which may interact with the host by a cross-talk mediated by intestinal miRNAs; phenomena that may contribute to amplify the metabolic derangement caused by obesity, as seen in neonatally androgenized female rats.

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Daniel M Kelly Department of Human Metabolism, Robert Hague Centre for Diabetes and Endocrinology, Medical School, The University of Sheffield, Sheffield S10 2RX, UK

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T Hugh Jones Department of Human Metabolism, Robert Hague Centre for Diabetes and Endocrinology, Medical School, The University of Sheffield, Sheffield S10 2RX, UK
Department of Human Metabolism, Robert Hague Centre for Diabetes and Endocrinology, Medical School, The University of Sheffield, Sheffield S10 2RX, UK

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type 2 diabetes mellitus (T2DM)) that are well known to be associated with an increased incidence of CVD. Atherosclerosis is a complex disease of the arteries characterised by endothelial dysfunction, vascular inflammation and the build-up of lipids

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Marcela Oliveira Departamento de Biofísica, Departmento de Microbiologia, Departamento de Fisiologia, Department of Oral Biological and Medical Sciences, Centro de Ciências Naturais e Humanas, Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, São Paulo, São Paulo 04039-032, Brazil

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Diego M Assis Departamento de Biofísica, Departmento de Microbiologia, Departamento de Fisiologia, Department of Oral Biological and Medical Sciences, Centro de Ciências Naturais e Humanas, Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, São Paulo, São Paulo 04039-032, Brazil

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Thaysa Paschoalin Departamento de Biofísica, Departmento de Microbiologia, Departamento de Fisiologia, Department of Oral Biological and Medical Sciences, Centro de Ciências Naturais e Humanas, Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, São Paulo, São Paulo 04039-032, Brazil

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Antonio Miranda Departamento de Biofísica, Departmento de Microbiologia, Departamento de Fisiologia, Department of Oral Biological and Medical Sciences, Centro de Ciências Naturais e Humanas, Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, São Paulo, São Paulo 04039-032, Brazil

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Eliane B Ribeiro Departamento de Biofísica, Departmento de Microbiologia, Departamento de Fisiologia, Department of Oral Biological and Medical Sciences, Centro de Ciências Naturais e Humanas, Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, São Paulo, São Paulo 04039-032, Brazil

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Maria A Juliano Departamento de Biofísica, Departmento de Microbiologia, Departamento de Fisiologia, Department of Oral Biological and Medical Sciences, Centro de Ciências Naturais e Humanas, Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, São Paulo, São Paulo 04039-032, Brazil

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Dieter Brömme Departamento de Biofísica, Departmento de Microbiologia, Departamento de Fisiologia, Department of Oral Biological and Medical Sciences, Centro de Ciências Naturais e Humanas, Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, São Paulo, São Paulo 04039-032, Brazil

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Marcelo Augusto Christoffolete Departamento de Biofísica, Departmento de Microbiologia, Departamento de Fisiologia, Department of Oral Biological and Medical Sciences, Centro de Ciências Naturais e Humanas, Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, São Paulo, São Paulo 04039-032, Brazil

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Nilana M T Barros Departamento de Biofísica, Departmento de Microbiologia, Departamento de Fisiologia, Department of Oral Biological and Medical Sciences, Centro de Ciências Naturais e Humanas, Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, São Paulo, São Paulo 04039-032, Brazil
Departamento de Biofísica, Departmento de Microbiologia, Departamento de Fisiologia, Department of Oral Biological and Medical Sciences, Centro de Ciências Naturais e Humanas, Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, São Paulo, São Paulo 04039-032, Brazil

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Adriana K Carmona Departamento de Biofísica, Departmento de Microbiologia, Departamento de Fisiologia, Department of Oral Biological and Medical Sciences, Centro de Ciências Naturais e Humanas, Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, São Paulo, São Paulo 04039-032, Brazil

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( Thomas et al . 2004 ), immune response, inflammation ( Lago et al . 2007 ), and atherosclerosis ( Taleb et al . 2007 ). The activities of leptin are mediated through its receptor (OB-R), which is encoded by the diabetes ( db ( Lepr )) gene on

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Mathias Fasshauer
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Johannes Klein
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Susan Kralisch
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Margit Klier
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Ulrike Lossner
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Matthias Bluher
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Ralf Paschke
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). Furthermore, the adipo-cytokine adiponectin has been established as both an endogenous insulin sensitizer and a protector of endothelial function diminishing the development of atherosclerosis ( Kubota et al. 2002 ). Moreover, various acute-phase reactants

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Jennifer J DuPont Molecular Cardiology Research Institute, Tufts Medical Center, Boston

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Iris Z Jaffe Molecular Cardiology Research Institute, Tufts Medical Center, Boston

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vascular remodeling & Stroke Unclear Vascular remodeling and vascular stiffness Lumen diameter reduction ( Dorrance et al. 2001 , McClain & Dorrance 2014 , Rigsby et al. 2007 ) Atherosclerosis & Myocardial Infarction EC Upregulation of

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Antonios Chatzigeorgiou Department of Experimental Physiology, Department of Internal Medicine III and Institute of Physiology, Department of Biological Chemistry, Endocrine Unit, Experimental Research Centre, University of Athens Medical School, Athens, Greece
Department of Experimental Physiology, Department of Internal Medicine III and Institute of Physiology, Department of Biological Chemistry, Endocrine Unit, Experimental Research Centre, University of Athens Medical School, Athens, Greece

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Eleni Kandaraki Department of Experimental Physiology, Department of Internal Medicine III and Institute of Physiology, Department of Biological Chemistry, Endocrine Unit, Experimental Research Centre, University of Athens Medical School, Athens, Greece
Department of Experimental Physiology, Department of Internal Medicine III and Institute of Physiology, Department of Biological Chemistry, Endocrine Unit, Experimental Research Centre, University of Athens Medical School, Athens, Greece

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Christina Piperi Department of Experimental Physiology, Department of Internal Medicine III and Institute of Physiology, Department of Biological Chemistry, Endocrine Unit, Experimental Research Centre, University of Athens Medical School, Athens, Greece

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Sarantis Livadas Department of Experimental Physiology, Department of Internal Medicine III and Institute of Physiology, Department of Biological Chemistry, Endocrine Unit, Experimental Research Centre, University of Athens Medical School, Athens, Greece

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Athanasios G Papavassiliou Department of Experimental Physiology, Department of Internal Medicine III and Institute of Physiology, Department of Biological Chemistry, Endocrine Unit, Experimental Research Centre, University of Athens Medical School, Athens, Greece

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Michael Koutsilieris Department of Experimental Physiology, Department of Internal Medicine III and Institute of Physiology, Department of Biological Chemistry, Endocrine Unit, Experimental Research Centre, University of Athens Medical School, Athens, Greece

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Apostolos Papalois Department of Experimental Physiology, Department of Internal Medicine III and Institute of Physiology, Department of Biological Chemistry, Endocrine Unit, Experimental Research Centre, University of Athens Medical School, Athens, Greece

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Evanthia Diamanti-Kandarakis Department of Experimental Physiology, Department of Internal Medicine III and Institute of Physiology, Department of Biological Chemistry, Endocrine Unit, Experimental Research Centre, University of Athens Medical School, Athens, Greece

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pathogenesis of other diseases such as atherosclerosis, chronic renal failure, polycystic ovary syndrome (PCOS) and Alzheimer's disease ( Mukhopadhyay & Mukherjee 2005 , Tan et al . 2011 ). Furthermore, data obtained from humans and experimental animals

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Kook Hwan Kim Severance Biomedical Research Institute, Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei‐ro, Seodaemun‐gu, Seoul 120-752, Korea

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Myung-Shik Lee Severance Biomedical Research Institute, Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei‐ro, Seodaemun‐gu, Seoul 120-752, Korea
Severance Biomedical Research Institute, Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei‐ro, Seodaemun‐gu, Seoul 120-752, Korea

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disease (CAD) and atherosclerosis. It has been reported that FGF21 was increased in the serum of human subjects with CAD and carotid artery plaques, and increased FGF21 levels were associated with adverse lipid profiles in CAD subjects ( Lin et al . 2010

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