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Abdominal Adipose Tissue Is Associated With Alterations in Tryptophan-Kynurenine Metabolism and Markers of Systemic Inflammation in People With Human Immunodeficiency Virus

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@article{12a92556b46b43f1bda1e6c97e8306b3,
title = "Abdominal Adipose Tissue Is Associated With Alterations in Tryptophan-Kynurenine Metabolism and Markers of Systemic Inflammation in People With Human Immunodeficiency Virus",
abstract = "BACKGROUND: While both adipose tissue accumulation and tryptophan metabolism alterations are features of human immunodeficiency virus (HIV) infection, their interplay is unclear. We investigated associations between abdominal adipose tissue, alterations in kynurenine pathway of tryptophan metabolism, and systemic inflammation in people with HIV (PWH). METHODS: Eight hundred sixty-four PWH and 75 uninfected controls were included. Plasma samples were collected and analyzed for kynurenine metabolites, neopterin, high-sensitivity C-reactive protein (hs-CRP), and lipids. Regression models were used to test associations in PWH. RESULTS: PWH had higher kynurenine-to-tryptophan ratio than uninfected individuals (P < .001). In PWH, increase in waist-to-hip ratio was associated with higher kynurenine-to-tryptophan ratio (P = .009) and quinolinic-to-kynurenic acid ratio (P = .006) and lower kynurenic acid concentration (P = .019). Quinolinic-to-kynurenic acid ratio was associated with higher hs-CRP (P < .001) and neopterin concentrations (P < .001), while kynurenic acid was associated with lower hs-CRP (P = .025) and neopterin concentrations (P = .034). CONCLUSIONS: In PWH, increase in abdominal adipose tissue was associated with increased quinolinic-to-kynurenic acid ratio, suggesting activation of proinflammatory pathway of kynurenine metabolism, with reduction of anti-inflammatory molecules and increase in systemic inflammation. Our results suggest dysregulation of kynurenine metabolism associated with abdominal fat accumulation to be a potential source of inflammation in HIV infection.",
keywords = "HIV infection, abdominal adipose tissue, inflammation, kynurenine, Quinolinic Acid/blood, Cross-Sectional Studies, Humans, Middle Aged, Kynurenic Acid/blood, C-Reactive Protein/analysis, Male, Kynurenine/metabolism, Inflammation/blood, Neopterin/blood, HIV Infections/metabolism, HIV, Abdominal Fat/metabolism, Biomarkers/blood, Female, Aged, Tryptophan/metabolism, Longitudinal Studies, Waist-Hip Ratio",
author = "Marco Gelpi and Ueland, {Per Magne} and Marius Tr{\o}seid and Amanda Mocroft and Anne-Mette Lebech and Henrik Ullum and {\O}ivind Midttun and Jens Lundgren and Nielsen, {Susanne D} and {Copenhagen Comorbidity in HIV Infection (COCOMO) Study}",
note = "{\circledC} The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.",
year = "2020",
month = "1",
day = "14",
doi = "10.1093/infdis/jiz465",
language = "English",
volume = "221",
pages = "419--427",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "University of Chicago Press",
number = "3",

}

RIS

TY - JOUR

T1 - Abdominal Adipose Tissue Is Associated With Alterations in Tryptophan-Kynurenine Metabolism and Markers of Systemic Inflammation in People With Human Immunodeficiency Virus

AU - Gelpi, Marco

AU - Ueland, Per Magne

AU - Trøseid, Marius

AU - Mocroft, Amanda

AU - Lebech, Anne-Mette

AU - Ullum, Henrik

AU - Midttun, Øivind

AU - Lundgren, Jens

AU - Nielsen, Susanne D

AU - Copenhagen Comorbidity in HIV Infection (COCOMO) Study

N1 - © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

PY - 2020/1/14

Y1 - 2020/1/14

N2 - BACKGROUND: While both adipose tissue accumulation and tryptophan metabolism alterations are features of human immunodeficiency virus (HIV) infection, their interplay is unclear. We investigated associations between abdominal adipose tissue, alterations in kynurenine pathway of tryptophan metabolism, and systemic inflammation in people with HIV (PWH). METHODS: Eight hundred sixty-four PWH and 75 uninfected controls were included. Plasma samples were collected and analyzed for kynurenine metabolites, neopterin, high-sensitivity C-reactive protein (hs-CRP), and lipids. Regression models were used to test associations in PWH. RESULTS: PWH had higher kynurenine-to-tryptophan ratio than uninfected individuals (P < .001). In PWH, increase in waist-to-hip ratio was associated with higher kynurenine-to-tryptophan ratio (P = .009) and quinolinic-to-kynurenic acid ratio (P = .006) and lower kynurenic acid concentration (P = .019). Quinolinic-to-kynurenic acid ratio was associated with higher hs-CRP (P < .001) and neopterin concentrations (P < .001), while kynurenic acid was associated with lower hs-CRP (P = .025) and neopterin concentrations (P = .034). CONCLUSIONS: In PWH, increase in abdominal adipose tissue was associated with increased quinolinic-to-kynurenic acid ratio, suggesting activation of proinflammatory pathway of kynurenine metabolism, with reduction of anti-inflammatory molecules and increase in systemic inflammation. Our results suggest dysregulation of kynurenine metabolism associated with abdominal fat accumulation to be a potential source of inflammation in HIV infection.

AB - BACKGROUND: While both adipose tissue accumulation and tryptophan metabolism alterations are features of human immunodeficiency virus (HIV) infection, their interplay is unclear. We investigated associations between abdominal adipose tissue, alterations in kynurenine pathway of tryptophan metabolism, and systemic inflammation in people with HIV (PWH). METHODS: Eight hundred sixty-four PWH and 75 uninfected controls were included. Plasma samples were collected and analyzed for kynurenine metabolites, neopterin, high-sensitivity C-reactive protein (hs-CRP), and lipids. Regression models were used to test associations in PWH. RESULTS: PWH had higher kynurenine-to-tryptophan ratio than uninfected individuals (P < .001). In PWH, increase in waist-to-hip ratio was associated with higher kynurenine-to-tryptophan ratio (P = .009) and quinolinic-to-kynurenic acid ratio (P = .006) and lower kynurenic acid concentration (P = .019). Quinolinic-to-kynurenic acid ratio was associated with higher hs-CRP (P < .001) and neopterin concentrations (P < .001), while kynurenic acid was associated with lower hs-CRP (P = .025) and neopterin concentrations (P = .034). CONCLUSIONS: In PWH, increase in abdominal adipose tissue was associated with increased quinolinic-to-kynurenic acid ratio, suggesting activation of proinflammatory pathway of kynurenine metabolism, with reduction of anti-inflammatory molecules and increase in systemic inflammation. Our results suggest dysregulation of kynurenine metabolism associated with abdominal fat accumulation to be a potential source of inflammation in HIV infection.

KW - HIV infection

KW - abdominal adipose tissue

KW - inflammation

KW - kynurenine

KW - Quinolinic Acid/blood

KW - Cross-Sectional Studies

KW - Humans

KW - Middle Aged

KW - Kynurenic Acid/blood

KW - C-Reactive Protein/analysis

KW - Male

KW - Kynurenine/metabolism

KW - Inflammation/blood

KW - Neopterin/blood

KW - HIV Infections/metabolism

KW - HIV

KW - Abdominal Fat/metabolism

KW - Biomarkers/blood

KW - Female

KW - Aged

KW - Tryptophan/metabolism

KW - Longitudinal Studies

KW - Waist-Hip Ratio

UR - http://www.scopus.com/inward/record.url?scp=85077942482&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiz465

DO - 10.1093/infdis/jiz465

M3 - Journal article

VL - 221

SP - 419

EP - 427

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 3

ER -

ID: 57996515