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
Obese individuals are at high risk of developing life-threatening co-morbidities. However, 10-25 % of obese people stay healthy. These individuals remain glucose tolerant and insulin sensitive, with normal blood pressure and a favorable lipid profile. Gerlini, Berti, and colleagues analyzed primary subcutaneous adipocytes from morbidly obese individuals discordant for metabolic health. They discovered that instead of insulin resistance, impaired glucose homeostasis is a major determinant of adipocyte transcriptional response. Furthermore, they identified 19 genetic associations with phenotypes of glucose homeostasis and/or body weight and composition.
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.