Marco Gelpi1, Per Magne Ueland2, Marius Trøseid3, Amanda Mocroft4, Anne-Mette Lebech5, Henrik Ullum6, Øivind Midttun2, Jens Lundgren1,7, Susanne D Nielsen1. 1. Viro-immunology Research Unit, Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 2. Section for Pharmacology, Department of Clinical Science, University of Bergen, Bergen, Norway. 3. Section of Clinical Immunology and Infectious Diseases, University Hospital Rikshospitalet, Oslo, Norway. 4. HIV Epidemiology and Biostatistics Unit, Department of Infection and Population Health, University College London, London, United Kingdom. 5. Department of Infectious Diseases, Hvidovre Hospital, Copenhagen University Hospital, Copenhagen, Denmark. 6. Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 7. Centre of Excellence for Health, Immunity and Infections, Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
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.
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.
Authors: Laiba Jamshed; Amrita Debnath; Shanza Jamshed; Jade V Wish; Jason C Raine; Gregg T Tomy; Philippe J Thomas; Alison C Holloway Journal: Int J Mol Sci Date: 2022-06-04 Impact factor: 6.208
Authors: Marco Gelpi; Flora Mikaeloff; Andreas D Knudsen; Rui Benfeitas; Shuba Krishnan; Sara Svenssson Akusjärvi; Julie Høgh; Daniel D Murray; Henrik Ullum; Ujjwal Neogi; Susanne D Nielsen Journal: Aging (Albany NY) Date: 2021-10-11 Impact factor: 5.682