TY - JOUR
T1 - An interferon-related signature characterizes the whole blood transcriptome profile of insulin-resistant individuals—the CODAM study
AU - Kalafati, Marianthi
AU - Kutmon, Martina
AU - Evelo, Chris T.
AU - van der Kallen, Carla J.H.
AU - Schalkwijk, Casper G.
AU - Stehouwer, Coen D.A.
AU - Blaak, Ellen E.
AU - van Greevenbroek, Marleen M.J.
AU - Adriaens, Michiel
AU - BIOS (Biobank-based Integrative Omics Study) Consortium
AU - Boomsma, Dorret
AU - Pool, René
AU - van Dongen, Jenny
AU - Hottenga, Jouke Jan
N1 - Funding Information:
The initiation of CODAM was supported by grants of the Netherlands Organization for Scientific Research (940-35-034) and the Dutch Diabetes Research Foundation (98-901). The Dutch province of Limburg supported part of this work (M. Adriaens, M. Kutmon).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: Worldwide, the prevalence of obesity and insulin resistance has grown dramatically. Gene expression profiling in blood represents a powerful means to explore disease pathogenesis, but the potential impact of inter-individual differences in a cell-type profile is not always taken into account. The objective of this project was to investigate the whole blood transcriptome profile of insulin-resistant as compared to insulin-sensitive individuals independent of inter-individual differences in white blood cell profile. Results: We report a 3% higher relative amount of monocytes in the insulin-resistant individuals. Furthermore, independent of their white blood cell profile, insulin-resistant participants had (i) higher expression of interferon-stimulated genes and (ii) lower expression of genes involved in cellular differentiation and remodeling of the actin cytoskeleton. Conclusions: We present an approach to investigate the whole blood transcriptome of insulin-resistant individuals, independent of their DNA methylation-derived white blood cell profile. An interferon-related signature characterizes the whole blood transcriptome profile of the insulin-resistant individuals, independent of their white blood cell profile. The observed signature indicates increased systemic inflammation possibly due to an innate immune response and whole-body insulin resistance, which can be a cause or a consequence of insulin resistance. Altered gene expression in specific organs may be reflected in whole blood; hence, our results may reflect obesity and/or insulin resistance-related organ dysfunction in the insulin-resistant individuals.
AB - Background: Worldwide, the prevalence of obesity and insulin resistance has grown dramatically. Gene expression profiling in blood represents a powerful means to explore disease pathogenesis, but the potential impact of inter-individual differences in a cell-type profile is not always taken into account. The objective of this project was to investigate the whole blood transcriptome profile of insulin-resistant as compared to insulin-sensitive individuals independent of inter-individual differences in white blood cell profile. Results: We report a 3% higher relative amount of monocytes in the insulin-resistant individuals. Furthermore, independent of their white blood cell profile, insulin-resistant participants had (i) higher expression of interferon-stimulated genes and (ii) lower expression of genes involved in cellular differentiation and remodeling of the actin cytoskeleton. Conclusions: We present an approach to investigate the whole blood transcriptome of insulin-resistant individuals, independent of their DNA methylation-derived white blood cell profile. An interferon-related signature characterizes the whole blood transcriptome profile of the insulin-resistant individuals, independent of their white blood cell profile. The observed signature indicates increased systemic inflammation possibly due to an innate immune response and whole-body insulin resistance, which can be a cause or a consequence of insulin resistance. Altered gene expression in specific organs may be reflected in whole blood; hence, our results may reflect obesity and/or insulin resistance-related organ dysfunction in the insulin-resistant individuals.
KW - Insulin resistance
KW - Inter-individual differences
KW - Interferon signature
KW - Monocytes
KW - Obesity
KW - Whole blood transcriptome
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U2 - 10.1186/s12263-021-00702-7
DO - 10.1186/s12263-021-00702-7
M3 - Article
AN - SCOPUS:85121012502
SN - 1555-8932
VL - 16
JO - Genes and Nutrition
JF - Genes and Nutrition
IS - 1
M1 - 22
ER -
