Abdominal fat mass is associated with adaptive immune activation: the CODAM study

M.M. Thewissen, J.G. Damoiseaux, A.M. Duijvestijn, M.M. Greevenbroek, C.J.H. van der Kallen, E.J.M. Feskens, E.E. Blaak, C.G. Schalkwijk, C.D.A. Stehouwer, J.W. Cohen Tervaert, I. Ferreira

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Abstract

Abdominal fat-related activation of the innate immune system and insulin resistance (IR) are implicated in the pathogenesis of cardiovascular diseases. Recent data support an important role of the adaptive immune system as well. In this study, we investigate the association between waist circumference and markers of systemic adaptive immune activation, and the potential mediating role of innate immune activation and/or IR herein. The study population consisted of 477 (304 men) individuals (mean age: 59.4 ± 7.0 years) in whom waist circumference, HOMA2-IR (IR derived from homeostasis model assessment), and markers of innate (C-reactive protein (CRP), interleukin (IL)-6, serum amyloid A (SAA)) and adaptive (neopterin, soluble CD25 (sCD25)) immune activation were measured. These markers were compiled into an adaptive and innate immune activation score by averaging the respective z-scores. After adjustments for age, sex, glucose metabolism, smoking status, prior cardiovascular disease, and other risk factors, waist circumference was associated with the adaptive (standardized regression coefficient ß = 0.12 (95% confidence intervals: 0.04-0.20)) and the innate immune activation scores (ß = 0.24 (0.17-0.31)), and with HOMA2-IR (ß = 0.49 (0.42-0.56)). The innate immune activation score and HOMA2-IR were also positively associated with the adaptive immune activation score (ß = 0.31 (0.21-0.40) and ß = 0.11 (0.02-0.21), respectively). The association between waist circumference and the adaptive immune activation score was completely abolished when further adjusted for innate immune activation and HOMA2-IR (to ß = -0.01 (-0.10-0.08)), and the specific mediation "effects" attributable to each of these variables were 58% and 42%, respectively. We conclude that abdominal obesity is associated with systemic adaptive immune activation and that innate immune activation and IR constitute independent and equally important pathways explaining this association
Original languageEnglish
Pages (from-to)1690-1698
JournalObesity
Volume19
Issue number8
DOIs
Publication statusPublished - 2011

Fingerprint

Abdominal Fat
Insulin Resistance
Waist Circumference
Immune System
Cardiovascular Diseases
Neopterin
Serum Amyloid A Protein
Abdominal Obesity
C-Reactive Protein
Interleukin-6
Homeostasis
Smoking
Confidence Intervals
Glucose

Keywords

  • adipose-tissue inflammation
  • ii-induced hypertension
  • c-reactive protein
  • effector t-cells
  • insulin-resistance
  • soluble interleukin-2-receptor
  • cardiovascular-disease
  • vascular dysfunction
  • metabolic syndrome
  • interferon-gamma

Cite this

Thewissen, M. M., Damoiseaux, J. G., Duijvestijn, A. M., Greevenbroek, M. M., van der Kallen, C. J. H., Feskens, E. J. M., ... Ferreira, I. (2011). Abdominal fat mass is associated with adaptive immune activation: the CODAM study. Obesity, 19(8), 1690-1698. https://doi.org/10.1038/oby.2010.337
Thewissen, M.M. ; Damoiseaux, J.G. ; Duijvestijn, A.M. ; Greevenbroek, M.M. ; van der Kallen, C.J.H. ; Feskens, E.J.M. ; Blaak, E.E. ; Schalkwijk, C.G. ; Stehouwer, C.D.A. ; Cohen Tervaert, J.W. ; Ferreira, I. / Abdominal fat mass is associated with adaptive immune activation: the CODAM study. In: Obesity. 2011 ; Vol. 19, No. 8. pp. 1690-1698.
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abstract = "Abdominal fat-related activation of the innate immune system and insulin resistance (IR) are implicated in the pathogenesis of cardiovascular diseases. Recent data support an important role of the adaptive immune system as well. In this study, we investigate the association between waist circumference and markers of systemic adaptive immune activation, and the potential mediating role of innate immune activation and/or IR herein. The study population consisted of 477 (304 men) individuals (mean age: 59.4 ± 7.0 years) in whom waist circumference, HOMA2-IR (IR derived from homeostasis model assessment), and markers of innate (C-reactive protein (CRP), interleukin (IL)-6, serum amyloid A (SAA)) and adaptive (neopterin, soluble CD25 (sCD25)) immune activation were measured. These markers were compiled into an adaptive and innate immune activation score by averaging the respective z-scores. After adjustments for age, sex, glucose metabolism, smoking status, prior cardiovascular disease, and other risk factors, waist circumference was associated with the adaptive (standardized regression coefficient {\ss} = 0.12 (95{\%} confidence intervals: 0.04-0.20)) and the innate immune activation scores ({\ss} = 0.24 (0.17-0.31)), and with HOMA2-IR ({\ss} = 0.49 (0.42-0.56)). The innate immune activation score and HOMA2-IR were also positively associated with the adaptive immune activation score ({\ss} = 0.31 (0.21-0.40) and {\ss} = 0.11 (0.02-0.21), respectively). The association between waist circumference and the adaptive immune activation score was completely abolished when further adjusted for innate immune activation and HOMA2-IR (to {\ss} = -0.01 (-0.10-0.08)), and the specific mediation {"}effects{"} attributable to each of these variables were 58{\%} and 42{\%}, respectively. We conclude that abdominal obesity is associated with systemic adaptive immune activation and that innate immune activation and IR constitute independent and equally important pathways explaining this association",
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author = "M.M. Thewissen and J.G. Damoiseaux and A.M. Duijvestijn and M.M. Greevenbroek and {van der Kallen}, C.J.H. and E.J.M. Feskens and E.E. Blaak and C.G. Schalkwijk and C.D.A. Stehouwer and {Cohen Tervaert}, J.W. and I. Ferreira",
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Thewissen, MM, Damoiseaux, JG, Duijvestijn, AM, Greevenbroek, MM, van der Kallen, CJH, Feskens, EJM, Blaak, EE, Schalkwijk, CG, Stehouwer, CDA, Cohen Tervaert, JW & Ferreira, I 2011, 'Abdominal fat mass is associated with adaptive immune activation: the CODAM study' Obesity, vol. 19, no. 8, pp. 1690-1698. https://doi.org/10.1038/oby.2010.337

Abdominal fat mass is associated with adaptive immune activation: the CODAM study. / Thewissen, M.M.; Damoiseaux, J.G.; Duijvestijn, A.M.; Greevenbroek, M.M.; van der Kallen, C.J.H.; Feskens, E.J.M.; Blaak, E.E.; Schalkwijk, C.G.; Stehouwer, C.D.A.; Cohen Tervaert, J.W.; Ferreira, I.

In: Obesity, Vol. 19, No. 8, 2011, p. 1690-1698.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Abdominal fat mass is associated with adaptive immune activation: the CODAM study

AU - Thewissen, M.M.

AU - Damoiseaux, J.G.

AU - Duijvestijn, A.M.

AU - Greevenbroek, M.M.

AU - van der Kallen, C.J.H.

AU - Feskens, E.J.M.

AU - Blaak, E.E.

AU - Schalkwijk, C.G.

AU - Stehouwer, C.D.A.

AU - Cohen Tervaert, J.W.

AU - Ferreira, I.

PY - 2011

Y1 - 2011

N2 - Abdominal fat-related activation of the innate immune system and insulin resistance (IR) are implicated in the pathogenesis of cardiovascular diseases. Recent data support an important role of the adaptive immune system as well. In this study, we investigate the association between waist circumference and markers of systemic adaptive immune activation, and the potential mediating role of innate immune activation and/or IR herein. The study population consisted of 477 (304 men) individuals (mean age: 59.4 ± 7.0 years) in whom waist circumference, HOMA2-IR (IR derived from homeostasis model assessment), and markers of innate (C-reactive protein (CRP), interleukin (IL)-6, serum amyloid A (SAA)) and adaptive (neopterin, soluble CD25 (sCD25)) immune activation were measured. These markers were compiled into an adaptive and innate immune activation score by averaging the respective z-scores. After adjustments for age, sex, glucose metabolism, smoking status, prior cardiovascular disease, and other risk factors, waist circumference was associated with the adaptive (standardized regression coefficient ß = 0.12 (95% confidence intervals: 0.04-0.20)) and the innate immune activation scores (ß = 0.24 (0.17-0.31)), and with HOMA2-IR (ß = 0.49 (0.42-0.56)). The innate immune activation score and HOMA2-IR were also positively associated with the adaptive immune activation score (ß = 0.31 (0.21-0.40) and ß = 0.11 (0.02-0.21), respectively). The association between waist circumference and the adaptive immune activation score was completely abolished when further adjusted for innate immune activation and HOMA2-IR (to ß = -0.01 (-0.10-0.08)), and the specific mediation "effects" attributable to each of these variables were 58% and 42%, respectively. We conclude that abdominal obesity is associated with systemic adaptive immune activation and that innate immune activation and IR constitute independent and equally important pathways explaining this association

AB - Abdominal fat-related activation of the innate immune system and insulin resistance (IR) are implicated in the pathogenesis of cardiovascular diseases. Recent data support an important role of the adaptive immune system as well. In this study, we investigate the association between waist circumference and markers of systemic adaptive immune activation, and the potential mediating role of innate immune activation and/or IR herein. The study population consisted of 477 (304 men) individuals (mean age: 59.4 ± 7.0 years) in whom waist circumference, HOMA2-IR (IR derived from homeostasis model assessment), and markers of innate (C-reactive protein (CRP), interleukin (IL)-6, serum amyloid A (SAA)) and adaptive (neopterin, soluble CD25 (sCD25)) immune activation were measured. These markers were compiled into an adaptive and innate immune activation score by averaging the respective z-scores. After adjustments for age, sex, glucose metabolism, smoking status, prior cardiovascular disease, and other risk factors, waist circumference was associated with the adaptive (standardized regression coefficient ß = 0.12 (95% confidence intervals: 0.04-0.20)) and the innate immune activation scores (ß = 0.24 (0.17-0.31)), and with HOMA2-IR (ß = 0.49 (0.42-0.56)). The innate immune activation score and HOMA2-IR were also positively associated with the adaptive immune activation score (ß = 0.31 (0.21-0.40) and ß = 0.11 (0.02-0.21), respectively). The association between waist circumference and the adaptive immune activation score was completely abolished when further adjusted for innate immune activation and HOMA2-IR (to ß = -0.01 (-0.10-0.08)), and the specific mediation "effects" attributable to each of these variables were 58% and 42%, respectively. We conclude that abdominal obesity is associated with systemic adaptive immune activation and that innate immune activation and IR constitute independent and equally important pathways explaining this association

KW - adipose-tissue inflammation

KW - ii-induced hypertension

KW - c-reactive protein

KW - effector t-cells

KW - insulin-resistance

KW - soluble interleukin-2-receptor

KW - cardiovascular-disease

KW - vascular dysfunction

KW - metabolic syndrome

KW - interferon-gamma

U2 - 10.1038/oby.2010.337

DO - 10.1038/oby.2010.337

M3 - Article

VL - 19

SP - 1690

EP - 1698

JO - Obesity

JF - Obesity

SN - 1930-7381

IS - 8

ER -

Thewissen MM, Damoiseaux JG, Duijvestijn AM, Greevenbroek MM, van der Kallen CJH, Feskens EJM et al. Abdominal fat mass is associated with adaptive immune activation: the CODAM study. Obesity. 2011;19(8):1690-1698. https://doi.org/10.1038/oby.2010.337