Evaluation of lipid metabolism imbalance in HIV-infected patients with metabolic disorders using high-performance liquid chromatography-tandem mass spectrometry

Zhang, Jing; Jin, Hongliu; Jian, Feng-Bi; Feng, Senling; Zhu, Wenting; Li, Linghua; Yuan, Zhongwen

doi:10.1016/j.cca.2021.12.010

Cited by 4 publications

(3 citation statements)

References 41 publications

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“…In accordance with previous reports, triglycerides were found to be increased in the plasma of HIV-infected mice, regardless of Mtb infection status 69 . Thus, Lysophosphatidylcholines (LysoPC), such as LysoPC (16:0/0:0), have been found to be increased in HIV-infected individuals 70 . Paradoxically, the concentration of palmitic acid (16:0), the fatty acid attached to the C-1 position of LysoPC (16:0/0:0), was found to be decreased in HIV-infected mice compared to the uninfected controls, suggesting a disruption in fatty acid metabolism.…”

Section: Discussionmentioning

confidence: 99%

A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies

Bohórquez,

Adduri,

Ansari

et al. 2024

Preprint

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. Further, co-infections with HIV and Mtb have severe effects in the host, with people infected with HIV being fifteen to twenty-one times more likely to develop active TB. The use of an appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans would be a useful tool for conducting basic and translational research in HIV/Mtb infections. The present study was focused on developing a humanized mouse model for investigations on HIV-Mtb co-infection. Using NSG-SGM3 mice that can engraft human stem cells, our studies showed that they were able to engraft human CD34+ stem cells which then differentiate into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced the development of granulomatous lesions in the lungs, detected by CT scan and histopathology. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections. Our results suggest that the humanized NSG-SGM3 mice are able to recapitulate the effects of HIV and Mtb infections and co-infection in the human host at pathological, immunological and metabolism levels, providing a dependable small animal model for studying HIV/Mtb co-infection.

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Section: Discussionmentioning

confidence: 99%

A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies

Bohórquez,

Adduri,

Ansari

et al. 2024

Preprint

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show abstract

“…In accordance with previous reports, triglycerides were found to be increased in the plasma of HIV-infected mice, regardless of Mtb infection status (87). Thus, Lysophosphatidylcholines (LysoPC), such as LysoPC (16:0/0:0), have been found to be increased in HIV-infected individuals (88). Paradoxically, the concentration of palmitic acid (16:0), the fatty acid attached to the C-1 position of LysoPC (16:0/ 0:0), was found to be decreased in HIV-infected mice compared to the uninfected controls, suggesting a disruption in fatty acid metabolism.…”

Section: Discussionmentioning

confidence: 99%

A novel humanized mouse model for HIV and tuberculosis co-infection studies

Bohórquez,

Adduri,

Ansari

et al. 2024

Front. Immunol.

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BackgroundTuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. HIV infection decreases CD4+ T cell levels markedly increasing Mtb co-infections. An appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans during co-infection would facilitate basic and translational research in HIV/Mtb infections. Herein, we describe a novel humanized mouse model.MethodsThe irradiated NSG-SGM3 mice were transplanted with human CD34+ hematopoietic stem cells, and the humanization was monitored by staining various immune cell markers for flow cytometry. They were challenged with HIV and/or Mtb, and the CD4+ T cell depletion and HIV viral load were monitored over time. Before necropsy, the live mice were subjected to pulmonary function test and CT scan, and after sacrifice, the lung and spleen homogenates were used to determine Mtb load (CFU) and cytokine/chemokine levels by multiplex assay, and lung sections were analyzed for histopathology. The mouse sera were subjected to metabolomics analysis.ResultsOur humanized NSG-SGM3 mice were able to engraft human CD34+ stem cells, which then differentiated into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced granulomatous lesions in the lungs. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections.ConclusionThe humanized NSG-SGM3 mice are able to recapitulate the pathogenic effects of HIV and Mtb infections and co-infection at the pathological, immunological and metabolism levels and are therefore a reproducible small animal model for studying HIV/Mtb co-infection.

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“…The evaluation of the calibration curve, recovery, matrix effect, accuracy and precision, and stability were performed according to the "Guidance for Industry -Bioanalysis Method Validation' (Food and Drug Administration, May 2018)" "USP 1010 Analytical Data-Interpretation and treatment" and "AOAC Guidelines for Single Laboratory Validation of Chemical Methods for Dietary Supplements and Botanicals" using phosphate buffer saline (PBS). [15][16][17][18] An AAAfree serum matrix was not available, we have tried used 5% bovine serum albumin in phosphate-buffered saline as a blank matrix, but the level of Phe, Trp, and Tyr in the system were still high (The peak area counts exceeds 10 5 ). Therefore, the PBS was used as an alternative matrix for method validation (Precision, accuracy, stability, repeatability, and recovery).…”

Section: Assay Validationmentioning

confidence: 99%

Evaluation of characteristic metabolites of aromatic amino acids in patients with HIV infection at different stages of disease

Yuan

Gan

Jin

et al. 2022

Clinical Laboratory Analysis

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Background: Acquired immune deficiency syndrome (AIDS), human immunodeficiency virus (HIV) infection, and antiretroviral therapy are usually associated with metabolic disorders. Screening for biomarkers to evaluate the progression of metabolic disorders is important for the diagnosis and treatment of HIV infection. This study aimed to establish and validate a method to quantify serum aromatic amino acid (AAA) metabolites as biomarkers of metabolic disorders in patients with HIV. Methods:The AAAs and metabolites were analyzed using high-performance liquid chromatography-tandem mass spectrometry. Pearson's correlation, heatmap, and receiver operating characteristic curve analyses were used for statistical analysis.Results: Under optimal detection conditions, the lower limits of phenylalanine (Phe), tryptophan (Trp), kynurenine (Kyn), tyrosine, phenylacetylglutamine (PAGln), and 5-hydroxytryptamine quantification reached 0.02, 0.02, 0.01, 0.02, 0.01, and 0.002 μg/ml, respectively, and the precision of intra-and inter-day was stay below 10.30%. Serum samples were stable for at least 6 months when stored at −80°C. The inter-group differences and associations between the biomarkers exhibited a particular volatility trend in PAGln, Trp, and Kyn metabolism in HIV-infected patients with metabolic syndrome. Conclusions:The developed method can be used for rapid and sensitive quantification of the AAA metabolism profile in vivo to further appraise the process of HIV infection, evaluate intervening measures, conduct mechanistic investigations, and further study the utility of PAGln, a characteristic metabolite of AAA, as a biomarker of HIV infection coupled with metabolic syndrome.

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Evaluation of lipid metabolism imbalance in HIV-infected patients with metabolic disorders using high-performance liquid chromatography-tandem mass spectrometry

Cited by 4 publications

References 41 publications

A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies

A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies

A novel humanized mouse model for HIV and tuberculosis co-infection studies

Evaluation of characteristic metabolites of aromatic amino acids in patients with HIV infection at different stages of disease

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