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

Gelpi, Marco; Ueland, Per Magne; Trøseid, Marius; Mocroft, Amanda; Lebech, Anne‐Mette; Ullum, Henrik; Midttun, Øivind; Lundgren, Jens D.; Nielsen, Susanne Dam

doi:10.1093/infdis/jiz465

Cited by 15 publications

(15 citation statements)

References 34 publications

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“…Furthermore, in the interaction analysis, we found that dietary tryptophan interacted with abdominal obesity on obesity risk and interacted with sex on T2D risk. Abdominal obesity has been reported to upregulate indoleamine 2, 3‐dioxygenase activity by chronic immune‐mediated inflammation and then decrease tryptophan availability for the synthesis of serotonin and melatonin, which are the key players in the caloric intake regulation (32,36). This provides evidence for our finding that dietary tryptophan decreased obesity risk, especially in those without abdominal obesity.…”

Section: Discussionmentioning

confidence: 99%

Dietary tryptophan and the risk of obesity and type 2 diabetes: Total effect and mediation effect of sleep duration

Wang

Liu

et al. 2022

Obesity

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During the past three decades, the prevalence of obesity and type 2 diabetes (T2D) has risen dramatically, with over 650 million people with obesity and 422 million people with diabetes according to the World Health Organization, which is expected to bring colossal strain to global health care (1). There is compelling evidence that diet along with other lifestyle factors is important for the prevention of obesity and T2D (2,3). The Global Burden of Disease consortium concluded that improper diet is responsible for more risk of obesity and T2D than any other risk factor globally, including smoking (4). Therefore, dietary management was suggested to be an efficient way to mitigate the burden of these diseases.Tryptophan, an essential amino acid that cannot be endogenously synthesized and thus needs to be supplied by diet, plays a key role in protein synthesis and multiple metabolic functions.Tryptophan is the sole precursor of biologically active compounds such as serotonin (5), which has been suggested to be involved in appetite and weight regulation and to modify the risk for obesity and eating disorders in numerous epidemiological studies (6,7). Previous

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Section: Discussionmentioning

confidence: 99%

Dietary tryptophan and the risk of obesity and type 2 diabetes: Total effect and mediation effect of sleep duration

Wang

Liu

et al. 2022

Obesity

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“…However, whether perturbed glutamate homeostasis is also involved in other non-AIDS-associated comorbidities like MetS is still unknown. Abdominal adipose tissue accumulation, a well-known determinant of MetS in PLWH, has been previously suggested to be associated with increase macrophage infiltration and activation [ 20 ]. It may be speculated that alterations in macrophage glutamate metabolism in the abdominal tissue are also involved in MetS in PLWH.…”

Section: Discussionmentioning

confidence: 99%

The central role of the glutamate metabolism in long-term antiretroviral treated HIV-infected individuals with metabolic syndrome

Gelpi

Mikaeloff

Knudsen

et al. 2021

Aging

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Metabolic syndrome (MetS) is a significant factor for cardiometabolic comorbidities in people living with HIV (PLWH) and a barrier to healthy aging. The long-term consequences of HIV-infection and combination antiretroviral therapy (cART) in metabolic reprogramming are unknown. In this study, we investigated metabolic alterations in well-treated PLWH with MetS to identify potential mechanisms behind the MetS phenotype using advanced statistical and machine learning algorithms. We included 200 PLWH from the Copenhagen Comorbidity in HIV-infection (COCOMO) study. PLWH were grouped into PLWH with MetS ( n = 100) defined according to the International Diabetes Federation (IDF) consensus worldwide definition of the MetS or without MetS ( n = 100). The untargeted plasma metabolomics was performed using ultra-high-performance liquid chromatography/mass spectrometry (UHPLC/MS/MS) and immune-phenotyping of Glut1 (glucose transporter), xCT (glutamate/cysteine transporter) and MCT1 (pyruvate/lactate transporter) by flow cytometry. We applied several conventional approaches, machine learning algorithms, and linear classification models to identify the biologically relevant metabolites associated with MetS in PLWH. Of the 877 identified biochemicals, 9% (76/877) differed significantly between PLWH with and without MetS (false discovery rate < 0.05). The majority belonged to amino acid metabolism (43%). A consensus identification by combining supervised and unsupervised methods indicated 11 biomarkers of MetS phenotype in PLWH. A weighted co-expression network identified seven communities of positively intercorrelated metabolites. A single community contained six of the potential biomarkers mainly related to glutamate metabolism. Transporter expression identified altered xCT and MCT in both lymphocytic and monocytic cells. Combining metabolomics and immune-phenotyping indicated altered glutamate metabolism associated with MetS in PLWH, which has clinical significance.

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“…Abdominal adipose tissue accumulation, a well-known determinant of MetS in PLWH, has been previously suggested to be associated with increase macrophage infiltration and activation. 26 It may be speculated that alterations in macrophage glutamate metabolism in the abdominal tissue are also involved in MetS in PLWH.…”

Section: Discussionmentioning

confidence: 99%

Central role of the glutamate metabolism in long-term antiretroviral treated HIV-infected individuals with metabolic syndrome: a cross-sectional cohort study

Gelpi

Mikaeloff

et al. 2021

Preprint

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Background: Metabolic syndrome (MetS) is one of the major factors for cardiometabolic comorbidities in people living with HIV (PLWH). The long-term consequences of HIV-infection and combination antiretroviral therapy (cART) in metabolic reprogramming are unknown. In this study, we aim to investigate metabolic alterations in long-term well-treated PLWH with MetS to identify the potential mechanism behind the MetS phenotype using advanced statistical and machine learning algorithms. Methods: We included 200 PLWH ≥40 years old from the Copenhagen Comorbidity in HIV-infection (COCOMO) study. PLWH were grouped into PLWH with MetS (n=100) and without MetS (n=100). The clinical data were collected from the COCOMO database and untargeted plasma metabolomics was performed using ultra-high-performance liquid chromatography/mass spectrometry (UHPLC/MS/MS). Both clinical characteristics and plasma samples were collected at study baseline. We applied several conventional approaches, machine learning algorithm and linear classification model to identify the biologically relevant metabolites associated with MetS in PLWH. Findings: A total of 877 characterized biochemicals were identified. Of these, 9% (76/877) biochemicals differed significantly between PLWH with and without MetS (false discovery rate <0.05). The majority belonged to the amino acid metabolism (n=33, 43%). A consensus identification by combining supervised and unsupervised methods indicates 11 biomarkers of MetS phenotype in PLWH, of which seven (63%) have higher abundance in PLWH with MetS compared to the PLWH without MetS. A weighted co-expression network by Leiden partitioning analysis identified seven communities of positively intercorrelated metabolites, of which a single community contained six of the potential biomarkers mainly related to glutamate metabolism (glutamate, 4-hydroxyglutamate, α-ketoglutamate and γ-glutamylglutamate). Interpretation: Altered amino acid metabolism is a central characteristic of PLWH with MetS and a potential central role for glutamate metabolism in establishing this phenotype is suggested.

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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

Cited by 15 publications

References 34 publications

Dietary tryptophan and the risk of obesity and type 2 diabetes: Total effect and mediation effect of sleep duration

Dietary tryptophan and the risk of obesity and type 2 diabetes: Total effect and mediation effect of sleep duration

The central role of the glutamate metabolism in long-term antiretroviral treated HIV-infected individuals with metabolic syndrome

Central role of the glutamate metabolism in long-term antiretroviral treated HIV-infected individuals with metabolic syndrome: a cross-sectional cohort study

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