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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Adult
  • Blood Glucose / metabolism
  • Blood Pressure
  • Case-Control Studies
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Fasting
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Ontology
  • Glucose Clamp Technique
  • Humans
  • Insulin / administration & dosage*
  • Insulin / metabolism
  • Insulin Resistance / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Annotation
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • Severity of Illness Index
  • Transcription, Genetic*
  • Triglycerides / blood


  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Insulin
  • Triglycerides