Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity

Kiymet Bozaoglu; Chantal Attard; Hemant Kulkarni; Nik Cummings; Vincent P. Diego; Melanie A. Carless; Katherine A. Shields; Matthew P. Johnson; Sudhir Kowlessur; Thomas D. Dyer; Anthony G. Comuzzie; Laura Almasy; Paul Zimmet; Eric K. Moses; Harald H.H Göring; Joanne E. Curran; John Blangero; Jeremy B.M Jowett

doi:10.1210/jc.2013-4475

Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity

Kiymet Bozaoglu, Chantal Attard, Hemant Kulkarni, Nik Cummings, Vincent P. Diego, Melanie A. Carless, Katherine A. Shields, Matthew P. Johnson, Sudhir Kowlessur, Thomas D. Dyer, Anthony G. Comuzzie, Laura Almasy, Paul Zimmet, Eric K. Moses, Harald H.H Göring, Joanne E. Curran, John Blangero, Jeremy B.M Jowett

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

14 Citations (Scopus)

Abstract

Context: Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity.Thepathogeneticandclinical influences of sIL1RAP are unknown. Copyright

Objective: The objective of the studywasto elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts.

Design, Setting, and Participants: The study was conducted in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42 families) and South Asians living in Mauritius, n = 230).

Main Outcome Measures: Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP levels were investigated using both a large-scale gene expression profiling study and a genome-wide association study.

Results: Asignificant decrease in plasma sIL1RAP levels were observed in obese subjects, even after adjustment for age and sex. The sIL1RAP levels demonstrated a strong inverse association with obesity measures in both populations. All associations were more significant in females. Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP transcript levels (NM-134470), showed evidence for shared genetic influences with obesity measures and were significantly associated with the rs2885373 single-nucleotide polymorphism (P = 6.7 = 10=23) within the IL1RAP gene.

Conclusions: Plasma sIL1RAP levels are reduced in obesity and can potentially act as biomarkers of obesity. Mechanistic studies are required to understand the exact contribution of sIL1RAP to the pathogenesis of obesity.

Original language	English
Pages (from-to)	3435-3443
Number of pages	9
Journal	The Journal of Clinical Endocrinology & Metabolism
Volume	99
Issue number	9
DOIs	https://doi.org/10.1210/jc.2013-4475
Publication status	Published - 1 Sept 2014
Externally published	Yes

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Bozaoglu, K., Attard, C., Kulkarni, H., Cummings, N., Diego, V. P., Carless, M. A., Shields, K. A., Johnson, M. P., Kowlessur, S., Dyer, T. D., Comuzzie, A. G., Almasy, L., Zimmet, P., Moses, E. K., Göring, H. H. H., Curran, J. E., Blangero, J., & Jowett, J. B. M. (2014). Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity. The Journal of Clinical Endocrinology & Metabolism, 99(9), 3435-3443. https://doi.org/10.1210/jc.2013-4475

@article{262617a5a9d34b559c1bef16fa2601de,

title = "Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity",

abstract = "Context: Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity.Thepathogeneticandclinical influences of sIL1RAP are unknown. CopyrightObjective: The objective of the studywasto elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts.Design, Setting, and Participants: The study was conducted in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42 families) and South Asians living in Mauritius, n = 230).Main Outcome Measures: Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP levels were investigated using both a large-scale gene expression profiling study and a genome-wide association study.Results: Asignificant decrease in plasma sIL1RAP levels were observed in obese subjects, even after adjustment for age and sex. The sIL1RAP levels demonstrated a strong inverse association with obesity measures in both populations. All associations were more significant in females. Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP transcript levels (NM-134470), showed evidence for shared genetic influences with obesity measures and were significantly associated with the rs2885373 single-nucleotide polymorphism (P = 6.7 = 10=23) within the IL1RAP gene.Conclusions: Plasma sIL1RAP levels are reduced in obesity and can potentially act as biomarkers of obesity. Mechanistic studies are required to understand the exact contribution of sIL1RAP to the pathogenesis of obesity.",

author = "Kiymet Bozaoglu and Chantal Attard and Hemant Kulkarni and Nik Cummings and Diego, {Vincent P.} and Carless, {Melanie A.} and Shields, {Katherine A.} and Johnson, {Matthew P.} and Sudhir Kowlessur and Dyer, {Thomas D.} and Comuzzie, {Anthony G.} and Laura Almasy and Paul Zimmet and Moses, {Eric K.} and G{\"o}ring, {Harald H.H} and Curran, {Joanne E.} and John Blangero and Jowett, {Jeremy B.M}",

year = "2014",

month = sep,

day = "1",

doi = "10.1210/jc.2013-4475",

language = "English",

volume = "99",

pages = "3435--3443",

journal = "The Journal of Clinical Endocrinology & Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press, USA",

number = "9",

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Bozaoglu, K, Attard, C, Kulkarni, H, Cummings, N, Diego, VP, Carless, MA, Shields, KA, Johnson, MP, Kowlessur, S, Dyer, TD, Comuzzie, AG, Almasy, L, Zimmet, P, Moses, EK, Göring, HHH, Curran, JE, Blangero, J & Jowett, JBM 2014, 'Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity', The Journal of Clinical Endocrinology & Metabolism, vol. 99, no. 9, pp. 3435-3443. https://doi.org/10.1210/jc.2013-4475

TY - JOUR

T1 - Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity

AU - Bozaoglu, Kiymet

AU - Attard, Chantal

AU - Kulkarni, Hemant

AU - Cummings, Nik

AU - Diego, Vincent P.

AU - Carless, Melanie A.

AU - Shields, Katherine A.

AU - Johnson, Matthew P.

AU - Kowlessur, Sudhir

AU - Dyer, Thomas D.

AU - Comuzzie, Anthony G.

AU - Almasy, Laura

AU - Zimmet, Paul

AU - Moses, Eric K.

AU - Göring, Harald H.H

AU - Curran, Joanne E.

AU - Blangero, John

AU - Jowett, Jeremy B.M

PY - 2014/9/1

Y1 - 2014/9/1

N2 - Context: Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity.Thepathogeneticandclinical influences of sIL1RAP are unknown. CopyrightObjective: The objective of the studywasto elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts.Design, Setting, and Participants: The study was conducted in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42 families) and South Asians living in Mauritius, n = 230).Main Outcome Measures: Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP levels were investigated using both a large-scale gene expression profiling study and a genome-wide association study.Results: Asignificant decrease in plasma sIL1RAP levels were observed in obese subjects, even after adjustment for age and sex. The sIL1RAP levels demonstrated a strong inverse association with obesity measures in both populations. All associations were more significant in females. Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP transcript levels (NM-134470), showed evidence for shared genetic influences with obesity measures and were significantly associated with the rs2885373 single-nucleotide polymorphism (P = 6.7 = 10=23) within the IL1RAP gene.Conclusions: Plasma sIL1RAP levels are reduced in obesity and can potentially act as biomarkers of obesity. Mechanistic studies are required to understand the exact contribution of sIL1RAP to the pathogenesis of obesity.

AB - Context: Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity.Thepathogeneticandclinical influences of sIL1RAP are unknown. CopyrightObjective: The objective of the studywasto elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts.Design, Setting, and Participants: The study was conducted in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42 families) and South Asians living in Mauritius, n = 230).Main Outcome Measures: Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP levels were investigated using both a large-scale gene expression profiling study and a genome-wide association study.Results: Asignificant decrease in plasma sIL1RAP levels were observed in obese subjects, even after adjustment for age and sex. The sIL1RAP levels demonstrated a strong inverse association with obesity measures in both populations. All associations were more significant in females. Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP transcript levels (NM-134470), showed evidence for shared genetic influences with obesity measures and were significantly associated with the rs2885373 single-nucleotide polymorphism (P = 6.7 = 10=23) within the IL1RAP gene.Conclusions: Plasma sIL1RAP levels are reduced in obesity and can potentially act as biomarkers of obesity. Mechanistic studies are required to understand the exact contribution of sIL1RAP to the pathogenesis of obesity.

UR - http://www.scopus.com/inward/record.url?scp=84907221081&partnerID=8YFLogxK

U2 - 10.1210/jc.2013-4475

DO - 10.1210/jc.2013-4475

M3 - Article

C2 - 24915116

AN - SCOPUS:84907221081

SN - 0021-972X

VL - 99

SP - 3435

EP - 3443

JO - The Journal of Clinical Endocrinology & Metabolism

JF - The Journal of Clinical Endocrinology & Metabolism

IS - 9

ER -

Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity

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