Relationship between monocyte/macrophage activation marker soluble CD163 and insulin resistance in obese and normal-weight subjects

Summary Context  The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown. Objective  To investigate a marker of macrophage activation, soluble CD163 (sCD163), in relationship to insulin resistance and metabolic parameters in obese and normal‐weight subjects. De...

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Published inClinical endocrinology (Oxford) Vol. 77; no. 3; pp. 385 - 390
Main Authors Zanni, Markella V., Burdo, Tricia H., Makimura, Hideo, Williams, Kenneth C., Grinspoon, Steven K.
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Publishing Ltd 01.09.2012
Blackwell
Wiley Subscription Services, Inc
Subjects
Adult
Antigens, CD - blood
Antigens, Differentiation, Myelomonocytic - blood
Biological and medical sciences
Biomarkers - blood
Body Weight - immunology
Case-Control Studies
Endocrinopathies
Female
Fundamental and applied biological sciences. Psychology
Humans
Hyperglycemia
Insulin
Insulin resistance
Insulin Resistance - immunology
Macrophage Activation - immunology
Male
Medical sciences
Metabolic diseases
Middle Aged
Obesity
Obesity - blood
Obesity - immunology
Obesity - pathology
Receptors, Cell Surface - blood
Vertebrates: endocrinology
Weight control
Endocrinopathy
Human
Obesity
Pancreatic hormone
Monocyte
Neutral insulin injection
Body weight
Nutrition disorder
Biological marker
Metabolic diseases
Corporal biometry
Activation
Normal
Insulin
Target tissue resistance
Insulin resistance
Endocrinology
Nutritional status
Macrophage
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Abstract Summary Context  The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown. Objective  To investigate a marker of macrophage activation, soluble CD163 (sCD163), in relationship to insulin resistance and metabolic parameters in obese and normal‐weight subjects. Design and Participants  Ninety‐five healthy subjects (65 obese and 30 normal‐weight) were studied. Plasma concentrations of sCD163 were assessed, as well as markers of glucose homeostasis, anthropometrics, cytokines and adipokines. The relationships between sCD163 and these parameters were investigated, and multiple regression modelling assessing the contribution of sCD163 to insulin resistance (HOMA‐IR) was performed. Results  Soluble CD163 was significantly increased in obese subjects compared with normal‐weight controls [974 (657, 1272) ng/ml vs 599 (423, 892) ng/ml, median (IQR); P < 0·0001]. sCD163 was strongly associated with HOMA‐IR (Spearman’s ρ = 0·37, P = 0·0003) and other metabolic parameters. In multiple regression modelling for log HOMA‐IR, sCD163 remained significantly associated (P = 0·005) controlling for known mediators of insulin resistance including age, gender, visceral adiposity and inflammatory markers (model R2 = 0·54, P < 0·0001). Additional nested multiple regression models for log HOMA‐IR showed that sCD163 added more than other adipokines and inflammatory markers to the prediction of HOMA‐IR. Conclusions  Monocyte/macrophage activation, as reflected by sCD163 levels, is strongly associated with HOMA‐IR in normal‐weight and obese subjects after controlling for known mediators of insulin resistance. Moreover, sCD163 adds to standard risk markers for predicting insulin resistance. These data suggest that monocyte/macrophage activation may be an important determinant of insulin resistance in obesity.
AbstractList The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown. To investigate a marker of macrophage activation, soluble CD163 (sCD163), in relationship to insulin resistance and metabolic parameters in obese and normal-weight subjects. Ninety-five healthy subjects (65 obese and 30 normal-weight) were studied. Plasma concentrations of sCD163 were assessed, as well as markers of glucose homeostasis, anthropometrics, cytokines and adipokines. The relationships between sCD163 and these parameters were investigated, and multiple regression modelling assessing the contribution of sCD163 to insulin resistance (HOMA-IR) was performed. Soluble CD163 was significantly increased in obese subjects compared with normal-weight controls [974 (657, 1272) ng/ml vs 599 (423, 892) ng/ml, median (IQR); P < 0·0001]. sCD163 was strongly associated with HOMA-IR (Spearman's ρ = 0·37, P = 0·0003) and other metabolic parameters. In multiple regression modelling for log HOMA-IR, sCD163 remained significantly associated (P = 0·005) controlling for known mediators of insulin resistance including age, gender, visceral adiposity and inflammatory markers (model R(2) = 0·54, P < 0·0001). Additional nested multiple regression models for log HOMA-IR showed that sCD163 added more than other adipokines and inflammatory markers to the prediction of HOMA-IR. Monocyte/macrophage activation, as reflected by sCD163 levels, is strongly associated with HOMA-IR in normal-weight and obese subjects after controlling for known mediators of insulin resistance. Moreover, sCD163 adds to standard risk markers for predicting insulin resistance. These data suggest that monocyte/macrophage activation may be an important determinant of insulin resistance in obesity.
Context The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown. Objective To investigate a marker of macrophage activation, soluble CD163 (sCD163), in relationship to insulin resistance and metabolic parameters in obese and normal-weight subjects. Design and Participants Ninety-five healthy subjects (65 obese and 30 normal-weight) were studied. Plasma concentrations of sCD163 were assessed, as well as markers of glucose homeostasis, anthropometrics, cytokines and adipokines. The relationships between sCD163 and these parameters were investigated, and multiple regression modelling assessing the contribution of sCD163 to insulin resistance (HOMA-IR) was performed. Results Soluble CD163 was significantly increased in obese subjects compared with normal-weight controls [974 (657, 1272) ng/ml vs 599 (423, 892)ng/ml, median (IQR); P<0.0001]. sCD163 was strongly associated with HOMA-IR (Spearman's rho =0.37, P=0.0003) and other metabolic parameters. In multiple regression modelling for log HOMA-IR, sCD163 remained significantly associated (P=0.005) controlling for known mediators of insulin resistance including age, gender, visceral adiposity and inflammatory markers (model R2=0.54, P<0.0001). Additional nested multiple regression models for log HOMA-IR showed that sCD163 added more than other adipokines and inflammatory markers to the prediction of HOMA-IR. Conclusions Monocyte/macrophage activation, as reflected by sCD163 levels, is strongly associated with HOMA-IR in normal-weight and obese subjects after controlling for known mediators of insulin resistance. Moreover, sCD163 adds to standard risk markers for predicting insulin resistance. These data suggest that monocyte/macrophage activation may be an important determinant of insulin resistance in obesity.
Summary Context  The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown. Objective  To investigate a marker of macrophage activation, soluble CD163 (sCD163), in relationship to insulin resistance and metabolic parameters in obese and normal‐weight subjects. Design and Participants  Ninety‐five healthy subjects (65 obese and 30 normal‐weight) were studied. Plasma concentrations of sCD163 were assessed, as well as markers of glucose homeostasis, anthropometrics, cytokines and adipokines. The relationships between sCD163 and these parameters were investigated, and multiple regression modelling assessing the contribution of sCD163 to insulin resistance (HOMA‐IR) was performed. Results  Soluble CD163 was significantly increased in obese subjects compared with normal‐weight controls [974 (657, 1272) ng/ml vs 599 (423, 892) ng/ml, median (IQR); P < 0·0001]. sCD163 was strongly associated with HOMA‐IR (Spearman’s ρ = 0·37, P = 0·0003) and other metabolic parameters. In multiple regression modelling for log HOMA‐IR, sCD163 remained significantly associated (P = 0·005) controlling for known mediators of insulin resistance including age, gender, visceral adiposity and inflammatory markers (model R2 = 0·54, P < 0·0001). Additional nested multiple regression models for log HOMA‐IR showed that sCD163 added more than other adipokines and inflammatory markers to the prediction of HOMA‐IR. Conclusions  Monocyte/macrophage activation, as reflected by sCD163 levels, is strongly associated with HOMA‐IR in normal‐weight and obese subjects after controlling for known mediators of insulin resistance. Moreover, sCD163 adds to standard risk markers for predicting insulin resistance. These data suggest that monocyte/macrophage activation may be an important determinant of insulin resistance in obesity.
The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown.CONTEXTThe relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown.To investigate a marker of macrophage activation, soluble CD163 (sCD163), in relationship to insulin resistance and metabolic parameters in obese and normal-weight subjects.OBJECTIVETo investigate a marker of macrophage activation, soluble CD163 (sCD163), in relationship to insulin resistance and metabolic parameters in obese and normal-weight subjects.Ninety-five healthy subjects (65 obese and 30 normal-weight) were studied. Plasma concentrations of sCD163 were assessed, as well as markers of glucose homeostasis, anthropometrics, cytokines and adipokines. The relationships between sCD163 and these parameters were investigated, and multiple regression modelling assessing the contribution of sCD163 to insulin resistance (HOMA-IR) was performed.DESIGN AND PARTICIPANTSNinety-five healthy subjects (65 obese and 30 normal-weight) were studied. Plasma concentrations of sCD163 were assessed, as well as markers of glucose homeostasis, anthropometrics, cytokines and adipokines. The relationships between sCD163 and these parameters were investigated, and multiple regression modelling assessing the contribution of sCD163 to insulin resistance (HOMA-IR) was performed.Soluble CD163 was significantly increased in obese subjects compared with normal-weight controls [974 (657, 1272) ng/ml vs 599 (423, 892) ng/ml, median (IQR); P < 0·0001]. sCD163 was strongly associated with HOMA-IR (Spearman's ρ = 0·37, P = 0·0003) and other metabolic parameters. In multiple regression modelling for log HOMA-IR, sCD163 remained significantly associated (P = 0·005) controlling for known mediators of insulin resistance including age, gender, visceral adiposity and inflammatory markers (model R(2) = 0·54, P < 0·0001). Additional nested multiple regression models for log HOMA-IR showed that sCD163 added more than other adipokines and inflammatory markers to the prediction of HOMA-IR.RESULTSSoluble CD163 was significantly increased in obese subjects compared with normal-weight controls [974 (657, 1272) ng/ml vs 599 (423, 892) ng/ml, median (IQR); P < 0·0001]. sCD163 was strongly associated with HOMA-IR (Spearman's ρ = 0·37, P = 0·0003) and other metabolic parameters. In multiple regression modelling for log HOMA-IR, sCD163 remained significantly associated (P = 0·005) controlling for known mediators of insulin resistance including age, gender, visceral adiposity and inflammatory markers (model R(2) = 0·54, P < 0·0001). Additional nested multiple regression models for log HOMA-IR showed that sCD163 added more than other adipokines and inflammatory markers to the prediction of HOMA-IR.Monocyte/macrophage activation, as reflected by sCD163 levels, is strongly associated with HOMA-IR in normal-weight and obese subjects after controlling for known mediators of insulin resistance. Moreover, sCD163 adds to standard risk markers for predicting insulin resistance. These data suggest that monocyte/macrophage activation may be an important determinant of insulin resistance in obesity.CONCLUSIONSMonocyte/macrophage activation, as reflected by sCD163 levels, is strongly associated with HOMA-IR in normal-weight and obese subjects after controlling for known mediators of insulin resistance. Moreover, sCD163 adds to standard risk markers for predicting insulin resistance. These data suggest that monocyte/macrophage activation may be an important determinant of insulin resistance in obesity.
Summary Context The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown. Objective To investigate a marker of macrophage activation, soluble CD163 (sCD163), in relationship to insulin resistance and metabolic parameters in obese and normal-weight subjects. Design and Participants Ninety-five healthy subjects (65 obese and 30 normal-weight) were studied. Plasma concentrations of sCD163 were assessed, as well as markers of glucose homeostasis, anthropometrics, cytokines and adipokines. The relationships between sCD163 and these parameters were investigated, and multiple regression modelling assessing the contribution of sCD163 to insulin resistance (HOMA-IR) was performed. Results Soluble CD163 was significantly increased in obese subjects compared with normal-weight controls [974 (657, 1272) ng/ml vs 599 (423, 892) ng/ml, median (IQR); P < 0·0001]. sCD163 was strongly associated with HOMA-IR (Spearman's ρ = 0·37, P = 0·0003) and other metabolic parameters. In multiple regression modelling for log HOMA-IR, sCD163 remained significantly associated (P = 0·005) controlling for known mediators of insulin resistance including age, gender, visceral adiposity and inflammatory markers (model R2 = 0·54, P < 0·0001). Additional nested multiple regression models for log HOMA-IR showed that sCD163 added more than other adipokines and inflammatory markers to the prediction of HOMA-IR. Conclusions Monocyte/macrophage activation, as reflected by sCD163 levels, is strongly associated with HOMA-IR in normal-weight and obese subjects after controlling for known mediators of insulin resistance. Moreover, sCD163 adds to standard risk markers for predicting insulin resistance. These data suggest that monocyte/macrophage activation may be an important determinant of insulin resistance in obesity. [PUBLICATION ABSTRACT]
Context  The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown. Objective  To investigate a marker of macrophage activation, soluble CD163 (sCD163), in relationship to insulin resistance and metabolic parameters in obese and normal‐weight subjects. Design and Participants  Ninety‐five healthy subjects (65 obese and 30 normal‐weight) were studied. Plasma concentrations of sCD163 were assessed, as well as markers of glucose homeostasis, anthropometrics, cytokines and adipokines. The relationships between sCD163 and these parameters were investigated, and multiple regression modelling assessing the contribution of sCD163 to insulin resistance (HOMA‐IR) was performed. Results  Soluble CD163 was significantly increased in obese subjects compared with normal‐weight controls [974 (657, 1272) ng/ml vs 599 (423, 892) ng/ml, median (IQR); P  < 0·0001]. sCD163 was strongly associated with HOMA‐IR (Spearman’s ρ = 0·37, P  = 0·0003) and other metabolic parameters. In multiple regression modelling for log HOMA‐IR, sCD163 remained significantly associated ( P  = 0·005) controlling for known mediators of insulin resistance including age, gender, visceral adiposity and inflammatory markers (model R 2  = 0·54, P  < 0·0001). Additional nested multiple regression models for log HOMA‐IR showed that sCD163 added more than other adipokines and inflammatory markers to the prediction of HOMA‐IR. Conclusions  Monocyte/macrophage activation, as reflected by sCD163 levels, is strongly associated with HOMA‐IR in normal‐weight and obese subjects after controlling for known mediators of insulin resistance. Moreover, sCD163 adds to standard risk markers for predicting insulin resistance. These data suggest that monocyte/macrophage activation may be an important determinant of insulin resistance in obesity.
Author Zanni, Markella V.
Grinspoon, Steven K.
Makimura, Hideo
Burdo, Tricia H.
Williams, Kenneth C.
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  surname: Zanni
  fullname: Zanni, Markella V.
  organization: Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital, Boston
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  givenname: Tricia H.
  surname: Burdo
  fullname: Burdo, Tricia H.
  organization: The Department of Biology, Boston College, Chestnut Hill, MA, USA
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  givenname: Hideo
  surname: Makimura
  fullname: Makimura, Hideo
  organization: Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital, Boston
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  givenname: Kenneth C.
  surname: Williams
  fullname: Williams, Kenneth C.
  organization: The Department of Biology, Boston College, Chestnut Hill, MA, USA
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  givenname: Steven K.
  surname: Grinspoon
  fullname: Grinspoon, Steven K.
  organization: Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital, Boston
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Issue 3
Keywords Endocrinopathy
Human
Obesity
Pancreatic hormone
Monocyte
Neutral insulin injection
Body weight
Nutrition disorder
Biological marker
Metabolic diseases
Corporal biometry
Activation
Normal
Insulin
Target tissue resistance
Insulin resistance
Endocrinology
Nutritional status
Macrophage
Language English
License http://onlinelibrary.wiley.com/termsAndConditions#vor
CC BY 4.0
2011 Blackwell Publishing Ltd.
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These authors contributed equally to this work.
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ObjectType-Article-1
ObjectType-Feature-2
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Authors contributed equally.
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2000; 102
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2008; 118
1999; 256
1995; 122
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2005; 39
2009; 39
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References_xml – reference: Schaer, D.J., Schleiffenbaum, B., Kurrer, M. et al. (2005) Soluble hemoglobin-haptoglobin scavenger receptor CD163 as a lineage-specific marker in the reactive hemophagocytic syndrome. European Journal of Haematology, 74, 6-10.
– reference: Aristoteli, L.P., Moller, H.J., Bailey, B. et al. (2006) The monocytic lineage specific soluble CD163 is a plasma marker of coronary atherosclerosis. Atherosclerosis, 184, 342-347.
– reference: Lohman, T.G., Roche, A.F. & Martorell, R., eds. (1988) Athropometric Standardization Reference Manual. Human Kinetic Books, Champaign, IL.
– reference: Etzerodt, A., Maniecki, M.B., Moller, K. et al. (2010) Tumor necrosis factor alpha-converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163. Journal of Leukocyte Biology, 88, 1201-1205.
– reference: Chan, J.M., Rimm, E.B., Colditz, G.A. et al. (1994) Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care, 17, 961-969.
– reference: Moller, H.J., Frikke-Schmidt, R., Moestrup, S.K. et al. (2011) Serum soluble CD163 predicts risk of type 2 diabetes in the general population. Clinical Chemistry, 57, 291-297.
– reference: Kristiansen, M., Graversen, J.H., Jacobsen, C. et al. (2001) Identification of the haemoglobin scavenger receptor. Nature, 409, 198-201.
– reference: Makimura, H., Stanley, T., Mun, D. et al. (2008) The effects of central adiposity on growth hormone (GH) response to GH-releasing hormone-arginine stimulation testing in men. Journal of Clinical Endocrinology and Metabolism, 93, 4254-4260.
– reference: Rietschel, P., Hadigan, C., Corcoran, C. et al. (2001) Assessment of growth hormone dynamics in human immunodeficiency virus-related lipodystrophy. Journal of Clinical Endocrinology and Metabolism, 86, 504-510.
– reference: Festa, A., D'Agostino R. Jr, Howard, G. et al. (2000) Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation, 102, 42-47.
– reference: Tsigos, C., Kyrou, I., Chala, E. et al. (1999) Circulating tumor necrosis factor alpha concentrations are higher in abdominal versus peripheral obesity. Metabolism, 48, 1332-1335.
– reference: Van Gorp, H., Delputte, P.L. & Nauwynck, H.J. (2010) Scavenger receptor CD163, a Jack-of-all-trades and potential target for cell-directed therapy. Molecular Immunology, 47, 1650-1660.
– reference: Moller, H.J., Peterslund, N.A., Graversen, J.H. et al. (2002) Identification of the hemoglobin scavenger receptor/CD163 as a natural soluble protein in plasma. Blood, 99, 378-380.
– reference: Zeyda, M., Farmer, D., Todoric, J. et al. (2007) Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. International Journal of Obesity, 31, 1420-1428.
– reference: Droste, A., Sorg, C. & Hogger, P. (1999) Shedding of CD163, a novel regulatory mechanism for a member of the scavenger receptor cysteine-rich family. Biochemical and Biophysical Research Communications, 256, 110-113.
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– reference: Sporrer, D., Weber, M., Wanninger, J. et al. (2009) Adiponectin downregulates CD163 whose cellular and soluble forms are elevated in obesity. European Journal of Clinical Investigation, 39, 671-679.
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Snippet Summary Context  The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown. Objective  To investigate a marker of...
Context  The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown. Objective  To investigate a marker of macrophage...
The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown. To investigate a marker of macrophage activation, soluble CD163...
Summary Context The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown. Objective To investigate a marker of macrophage...
The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown.CONTEXTThe relationship of monocyte/macrophage activation to...
Context The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown. Objective To investigate a marker of macrophage...
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StartPage 385
SubjectTerms Adult
Antigens, CD - blood
Antigens, Differentiation, Myelomonocytic - blood
Biological and medical sciences
Biomarkers - blood
Body Weight - immunology
Case-Control Studies
Endocrinopathies
Female
Fundamental and applied biological sciences. Psychology
Humans
Hyperglycemia
Insulin
Insulin resistance
Insulin Resistance - immunology
Macrophage Activation - immunology
Male
Medical sciences
Metabolic diseases
Middle Aged
Obesity
Obesity - blood
Obesity - immunology
Obesity - pathology
Receptors, Cell Surface - blood
Vertebrates: endocrinology
Weight control
Title Relationship between monocyte/macrophage activation marker soluble CD163 and insulin resistance in obese and normal-weight subjects
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https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1365-2265.2011.04284.x
https://www.ncbi.nlm.nih.gov/pubmed/22098563
https://www.proquest.com/docview/1545891878
https://www.proquest.com/docview/1033682732
https://www.proquest.com/docview/1897373996
https://pubmed.ncbi.nlm.nih.gov/PMC3660104
Volume 77
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