An interferon-related signature characterizes the whole blood transcriptome profile of insulin-resistant individuals-the CODAM study

Marianthi Kalafati; Martina Kutmon; Chris T. Evelo; Carla J. H. van der Kallen; Casper G. Schalkwijk; Coen D. A. Stehouwer; Ellen E. Blaak; Marleen M. J. van Greevenbroek; Michiel Adriaens; BIOS Consortium

doi:10.1186/s12263-021-00702-7

An interferon-related signature characterizes the whole blood transcriptome profile of insulin-resistant individuals-the CODAM study

Marianthi Kalafati, Martina Kutmon, Chris T. Evelo, Carla J. H. van der Kallen, Casper G. Schalkwijk, Coen D. A. Stehouwer, Ellen E. Blaak, Marleen M. J. van Greevenbroek^*, Michiel Adriaens, BIOS Consortium

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	22
Number of pages	13
Journal	Genes and nutrition
Volume	16
Issue number	1
DOIs	https://doi.org/10.1186/s12263-021-00702-7
Publication status	Published - 9 Dec 2021

Keywords

Insulin resistance
Obesity
Whole blood transcriptome
Monocytes
Inter-individual differences
Interferon signature
T-CELLS
EXPRESSION
INFLAMMATION
OBESE
HYPERGLYCEMIA
RECRUITMENT
PACKAGE

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Kalafati, M., Kutmon, M., Evelo, C. T., van der Kallen, C. J. H., Schalkwijk, C. G., Stehouwer, C. D. A., Blaak, E. E., van Greevenbroek, M. M. J., Adriaens, M., & BIOS Consortium (2021). An interferon-related signature characterizes the whole blood transcriptome profile of insulin-resistant individuals-the CODAM study. Genes and nutrition, 16(1), Article 22. https://doi.org/10.1186/s12263-021-00702-7

@article{501fbc2905094966a16d5e9470ba4e41,

title = "An interferon-related signature characterizes the whole blood transcriptome profile of insulin-resistant individuals-the CODAM study",

abstract = "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.",

keywords = "Insulin resistance, Obesity, Whole blood transcriptome, Monocytes, Inter-individual differences, Interferon signature, T-CELLS, EXPRESSION, INFLAMMATION, OBESE, HYPERGLYCEMIA, RECRUITMENT, PACKAGE",

author = "Marianthi Kalafati and Martina Kutmon and Evelo, {Chris T.} and {van der Kallen}, {Carla J. H.} and Schalkwijk, {Casper G.} and Stehouwer, {Coen D. A.} and Blaak, {Ellen E.} and {van Greevenbroek}, {Marleen M. J.} and Michiel Adriaens and {BIOS Consortium}",

note = "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: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

day = "9",

doi = "10.1186/s12263-021-00702-7",

language = "English",

volume = "16",

journal = "Genes and nutrition",

issn = "1555-8932",

publisher = "BioMed Central Ltd",

number = "1",

}

Kalafati, M, Kutmon, M , Evelo, CT , van der Kallen, CJH , Schalkwijk, CG, Stehouwer, CDA, Blaak, EE , van Greevenbroek, MMJ , Adriaens, M & BIOS Consortium 2021, 'An interferon-related signature characterizes the whole blood transcriptome profile of insulin-resistant individuals-the CODAM study', Genes and nutrition, vol. 16, no. 1, 22. https://doi.org/10.1186/s12263-021-00702-7

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 Consortium

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 - 2021/12/9

Y1 - 2021/12/9

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 - Obesity

KW - Whole blood transcriptome

KW - Monocytes

KW - Inter-individual differences

KW - Interferon signature

KW - T-CELLS

KW - EXPRESSION

KW - INFLAMMATION

KW - OBESE

KW - HYPERGLYCEMIA

KW - RECRUITMENT

KW - PACKAGE

U2 - 10.1186/s12263-021-00702-7

DO - 10.1186/s12263-021-00702-7

M3 - Article

C2 - 34886800

SN - 1555-8932

VL - 16

JO - Genes and nutrition

JF - Genes and nutrition

IS - 1

M1 - 22

ER -

An interferon-related signature characterizes the whole blood transcriptome profile of insulin-resistant individuals-the CODAM study

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Keywords

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