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Cell Rep. 2016 Aug 30;16(9):2317-26. doi: 10.1016/j.celrep.2016.07.070. Epub 2016 Aug 18.

The Adipose Transcriptional Response to Insulin Is Determined by Obesity, Not Insulin Sensitivity.

Author information

1
Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden.
2
Bioinformatics Short-term Support and Infrastructure (BILS), Science for Life Laboratory, Tomtebodavägen 23A, 171 65 Solna, Sweden.
3
Department of Biosciences and Nutrition, Science for Life Laboratory, Karolinska Institutet, 141 83 Huddinge, Sweden.
4
The Bioinformatics Centre, Department of Biology, Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen N, Denmark.
5
Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden; Department of Medicine, Ersta Hospital, Karolinska Institutet, 116 91 Stockholm, Sweden.
6
Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88 Stockholm, Sweden.
7
Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88 Stockholm, Sweden; Department of Surgery, Ersta Hospital, Karolinska Institutet, 116 91 Stockholm, Sweden.
8
Department of Biosciences and Nutrition, Karolinska Institutet, 141 86 Stockholm, Sweden.
9
Department of Biosciences and Nutrition, Science for Life Laboratory, Karolinska Institutet, 141 83 Huddinge, Sweden. Electronic address: carsten.daub@ki.se.
10
Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden. Electronic address: peter.arner@ki.se.

Abstract

Metabolically healthy obese subjects display preserved insulin sensitivity and a beneficial white adipose tissue gene expression pattern. However, this observation stems from fasting studies when insulin levels are low. We investigated adipose gene expression by 5'Cap-mRNA sequencing in 17 healthy non-obese (NO), 21 insulin-sensitive severely obese (ISO), and 30 insulin-resistant severely obese (IRO) subjects, before and 2 hr into a hyperinsulinemic euglycemic clamp. ISO and IRO subjects displayed a clear but globally similar transcriptional response to insulin, which differed from the small effects observed in NO subjects. In the obese, 231 genes were altered; 71 were enriched in ISO subjects (e.g., phosphorylation processes), and 52 were enriched in IRO subjects (e.g., cellular stimuli). Common cardio-metabolic risk factors and gender do not influence these findings. This study demonstrates that differences in the acute transcriptional response to insulin are primarily driven by obesity per se, challenging the notion of healthy obese adipose tissue, at least in severe obesity.

PMID:
27545890
DOI:
10.1016/j.celrep.2016.07.070
[Indexed for MEDLINE]
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