Glucose tolerance and insulin sensitivity define adipocyte transcriptional programs in human obesity

R. Gerlini; L. Berti; J. Darr; M. Lassi; S. Brandmaier; L. Fritsche; F. Scheid; A. Böhm; A. Königsrainer; H. Grallert; H.U. Häring; M. Hrabě de Angelis; H. Staiger; R. Teperino

Molecular Metabolism (Dec 2018)

Glucose tolerance and insulin sensitivity define adipocyte transcriptional programs in human obesity

R. Gerlini,
L. Berti,
J. Darr,
M. Lassi,
S. Brandmaier,
L. Fritsche,
F. Scheid,
A. Böhm,
A. Königsrainer,
H. Grallert,
H.U. Häring,
M. Hrabě de Angelis,
H. Staiger,
R. Teperino

Affiliations

R. Gerlini: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research center for Environmental Health – Neuherberg, Germany; German Center for Diabetes Research (DZD) – Neuherberg, Germany
L. Berti: German Center for Diabetes Research (DZD) – Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tübingen, Tübingen, Germany
J. Darr: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research center for Environmental Health – Neuherberg, Germany; German Center for Diabetes Research (DZD) – Neuherberg, Germany
M. Lassi: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research center for Environmental Health – Neuherberg, Germany; German Center for Diabetes Research (DZD) – Neuherberg, Germany
S. Brandmaier: German Center for Diabetes Research (DZD) – Neuherberg, Germany; Research Unit Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology 2, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany
L. Fritsche: German Center for Diabetes Research (DZD) – Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tübingen, Tübingen, Germany
F. Scheid: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research center for Environmental Health – Neuherberg, Germany; German Center for Diabetes Research (DZD) – Neuherberg, Germany
A. Böhm: German Center for Diabetes Research (DZD) – Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tübingen, Tübingen, Germany; Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany
A. Königsrainer: Department of General, Visceral and Transplant Surgery, University of Tübingen, Tübingen, Germany
H. Grallert: German Center for Diabetes Research (DZD) – Neuherberg, Germany; Research Unit Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology 2, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany
H.U. Häring: German Center for Diabetes Research (DZD) – Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tübingen, Tübingen, Germany; Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany
M. Hrabě de Angelis: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research center for Environmental Health – Neuherberg, Germany; German Center for Diabetes Research (DZD) – Neuherberg, Germany; Experimental Genetics, Faculty of Life and Food Sciences Weihenstephan, Technische Universität München, Freising-Weihenstephan, Germany
H. Staiger: German Center for Diabetes Research (DZD) – Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tübingen, Tübingen, Germany; Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, University of Tübingen, Tübingen, Germany; Corresponding author. German Center for Diabetes Research (DZD) – Neuherberg, Germany.
R. Teperino: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research center for Environmental Health – Neuherberg, Germany; German Center for Diabetes Research (DZD) – Neuherberg, Germany; Corresponding author.

Journal volume & issue: Vol. 18
pp. 42 – 50

Abstract

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Objective: Although debated, metabolic health characterizes 10–25% of obese individuals and reduces risk of developing life-threatening co-morbidities. Adipose tissue is a recognized endocrine organ important for the maintenance of whole-body metabolic health. Adipocyte transcriptional signatures of healthy and unhealthy obesity are largely unknown. Methods: Here, we used a small cohort of highly characterized obese individuals discordant for metabolic health, characterized their adipocytes transcriptional signatures, and cross-referenced them to mouse phenotypic and human GWAs databases. Results and conclusions: Our study showed that glucose intolerance and insulin resistance co-operate to remodel adipocyte transcriptome. We also identified the Nuclear Export Mediator Factor (NEMF) and the Ectoderm-Neural Cortex 1 (ENC1) as novel potential targets in the management of metabolic health in human obesity. Keywords: Obesity, Glucose tolerance, Insulin sensitivity, Transcriptomics, Mouse genetics, Systemic phenotyping

Published in Molecular Metabolism

ISSN: 2212-8778 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine
Website: https://www.journals.elsevier.com/molecular-metabolism/

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