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

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

doi:10.1016/j.celrep.2016.07.070

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

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

Bioinformatik og RNA Biologi

23 Citationer (Scopus)

138 Downloads (Pure)

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.

Originalsprog	Engelsk
Tidsskrift	Cell Reports
Vol/bind	16
Udgave nummer	9
Sider (fra-til)	2317-2326
Antal sider	10
DOI	https://doi.org/10.1016/j.celrep.2016.07.070
Status	Udgivet - 30 aug. 2016

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10.1016/j.celrep.2016.07.070Licens: CC BY-NC-ND

Ryden_2016_The_adipose_transcriptionalForlagets udgivne version, 1,73 MBLicens: CC BY-NC-ND

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Rydén, M., Hrydziuszko, O., Mileti, E., Raman, A., Lange, J. B., Boyd, M., Toft, E., Qvist, V., Näslund, E., Thorell, A., Andersson, D. P., Dahlman, I., Gao, H., Sandelin, A. G., Daub, C. O., & Arner, P. (2016). The adipose transcriptional response to insulin is determined by obesity, not insulin sensitivity. Cell Reports, 16(9), 2317-2326. https://doi.org/10.1016/j.celrep.2016.07.070

Rydén, M, Hrydziuszko, O, Mileti, E, Raman, A, Lange, JB, Boyd, M, Toft, E, Qvist, V, Näslund, E, Thorell, A, Andersson, DP, Dahlman, I, Gao, H, Sandelin, AG, Daub, CO & Arner, P 2016, 'The adipose transcriptional response to insulin is determined by obesity, not insulin sensitivity', Cell Reports, bind 16, nr. 9, s. 2317-2326. https://doi.org/10.1016/j.celrep.2016.07.070

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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.",

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AU - Rydén, Mikael

AU - Hrydziuszko, Olga

AU - Mileti, Enrichetta

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AU - Lange, Jette Bornholdt

AU - Boyd, Mette

AU - Toft, Eva

AU - Qvist, Veronica

AU - Näslund, Erik

AU - Thorell, Anders

AU - Andersson, Daniel P.

AU - Dahlman, Ingrid

AU - Gao, Hui

AU - Sandelin, Albin Gustav

AU - Daub, Carsten O.

AU - Arner, Peter

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N2 - 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.

AB - 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.

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

Abstract

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