title: The Adipose Transcriptional Response to Insulin Is Determined by Obesity, Not Insulin Sensitivity.
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.
authors.affiliation: Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Rydén
authors.affiliation: Bioinformatics Short-term Support and Infrastructure (BILS), Science for Life Laboratory, Tomtebodavägen 23A, 171 65 Solna, Sweden.
authors.forename: Olga
authors.initials: O
authors.lastname: Hrydziuszko
authors.affiliation: Department of Biosciences and Nutrition, Science for Life Laboratory, Karolinska Institutet, 141 83 Huddinge, Sweden.
authors.forename: Enrichetta
authors.initials: E
authors.lastname: Mileti
authors.affiliation: Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden.
authors.forename: Amitha
authors.initials: A
authors.lastname: Raman
authors.affiliation: The Bioinformatics Centre, Department of Biology, Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen N, Denmark.
authors.forename: Jette
authors.initials: J
authors.lastname: Bornholdt
authors.affiliation: The Bioinformatics Centre, Department of Biology, Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen N, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Boyd
authors.affiliation: Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden; Department of Medicine, Ersta Hospital, Karolinska Institutet, 116 91 Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Toft
authors.affiliation: Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden; Department of Medicine, Ersta Hospital, Karolinska Institutet, 116 91 Stockholm, Sweden.
authors.forename: Veronica
authors.initials: V
authors.lastname: Qvist
authors.affiliation: Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88 Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Näslund
authors.affiliation: Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88 Stockholm, Sweden; Department of Surgery, Ersta Hospital, Karolinska Institutet, 116 91 Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Thorell
authors.affiliation: Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Andersson
authors.affiliation: Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden; Department of Medicine, Ersta Hospital, Karolinska Institutet, 116 91 Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, 141 86 Stockholm, Sweden.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: The Bioinformatics Centre, Department of Biology, Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen N, Denmark.
authors.forename: Albin
authors.initials: A
authors.lastname: Sandelin
authors.affiliation: Department of Biosciences and Nutrition, Science for Life Laboratory, Karolinska Institutet, 141 83 Huddinge, Sweden. Electronic address: carsten.daub@ki.se.
authors.forename: Carsten O
authors.initials: CO
authors.lastname: Daub
authors.affiliation: Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden. Electronic address: peter.arner@ki.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005215:Fasting; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D014158:Transcription, Genetic; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007328:Insulin; D014280:Triglycerides