The adipose transcriptional response to insulin is determined by obesity, not insulin sensitivity

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  • Mikael Rydén
  • Olga Hrydziuszko
  • Enrichetta Mileti
  • Amitha Raman
  • Lange, Jette Bornholdt
  • Mette Boyd
  • Eva Toft
  • Veronica Qvist
  • Erik Näslund
  • Anders Thorell
  • Daniel P. Andersson
  • Ingrid Dahlman
  • Hui Gao
  • Sandelin, Albin Gustav
  • Carsten O. Daub
  • Peter Arner

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.

Original languageEnglish
JournalCell Reports
Issue number9
Pages (from-to)2317-2326
Number of pages10
Publication statusPublished - 2016

    Research areas

  • Journal Article

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