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

doi:10.1016/j.molmet.2018.09.004

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

Mol Metab. 2018 Dec:18:42-50. doi: 10.1016/j.molmet.2018.09.004. Epub 2018 Sep 19.

Authors

R Gerlini¹, L Berti², J Darr¹, M Lassi¹, S Brandmaier³, L Fritsche², F Scheid¹, A Böhm⁴, A Königsrainer⁵, H Grallert³, H U Häring⁴, M Hrabě de Angelis⁶, H Staiger⁷, R Teperino⁸

Affiliations

¹ Institute of Experimental Genetics, Helmholtz Zentrum München, German Research center for Environmental Health - Neuherberg, Germany; German Center for Diabetes Research (DZD) - Neuherberg, Germany.
² 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.
³ 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.
⁴ 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.
⁵ Department of General, Visceral and Transplant Surgery, University of Tübingen, Tübingen, Germany.
⁶ 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.
⁷ 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. Electronic address: [email protected].
⁸ Institute of Experimental Genetics, Helmholtz Zentrum München, German Research center for Environmental Health - Neuherberg, Germany; German Center for Diabetes Research (DZD) - Neuherberg, Germany. Electronic address: [email protected].

Abstract

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: Glucose tolerance; Insulin sensitivity; Mouse genetics; Obesity; Systemic phenotyping; Transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes / metabolism*
Adult
Antigens, Neoplasm / genetics
Antigens, Neoplasm / metabolism
Cells, Cultured
Female
Glucose Intolerance*
Humans
Insulin Resistance*
Male
Microfilament Proteins / genetics
Microfilament Proteins / metabolism
Middle Aged
Neuropeptides / genetics
Neuropeptides / metabolism
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Nucleocytoplasmic Transport Proteins / genetics
Nucleocytoplasmic Transport Proteins / metabolism
Obesity / genetics
Obesity / metabolism*
Transcriptome*

Substances

Antigens, Neoplasm
Microfilament Proteins
NEMF protein, human
Neuropeptides
Nuclear Proteins
Nucleocytoplasmic Transport Proteins
ectodermal-neural cortex 1 protein