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1. Single-cell analysis shows that adipose tissue of persons with both HIV and diabetes is enriched for clonal, cytotoxic, and CMV-specific CD4+ T cells

Author

Wanjalla, Celestine N., McDonnell, Wyatt J., Ram, Ramesh, Chopra, Abha, Gangula, Rama, Leary, Shay, Mashayekhi, Mona, Simmons, Joshua D., Warren, Christian M., Bailin, Samuel, Gabriel, Curtis L., Guo, Liang, Furch, Briana D., Lima, Morgan C., Woodward, Beverly O., Hannah, LaToya, Pilkinton, Mark A., Fuller, Daniela T., Kawai, Kenji, Virmani, Renu, Finn, Aloke V., Hasty, Alyssa H., Mallal, Simon A., Kalams, Spyros A., and Koethe, John R.

Published
2021
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3. Changes in subcutaneous white adipose tissue cellular composition and molecular programs underlie glucose intolerance in persons with HIV

Author

Bailin, Samuel S., primary, Kropski, Jonathan A., additional, Gangula, Rama D., additional, Hannah, LaToya, additional, Simmons, Joshua D., additional, Mashayekhi, Mona, additional, Ye, Fei, additional, Fan, Run, additional, Mallal, Simon, additional, Warren, Christian M., additional, Kalams, Spyros A., additional, Gabriel, Curtis L., additional, Wanjalla, Celestine N., additional, and Koethe, John R., additional

Published
2023
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4. Mean Coronary Cross‐Sectional Area as a Measure of Arterial Remodeling Using Noncontrast CT Imaging in Persons With HIV

Author

Werede, Ayoda T., primary, Terry, James G., additional, Nair, Sangeeta, additional, Temu, Tecla M., additional, Shepherd, Bryan E., additional, Bailin, Samuel S., additional, Mashayekhi, Mona, additional, Gabriel, Curtis L., additional, Lima, Morgan, additional, Woodward, Beverly Owen, additional, Hannah, LaToya, additional, Mallal, Simon A., additional, Beckman, Joshua A., additional, Li, Jonathan Z., additional, Fajnzylber, Jesse, additional, Harrison, David G., additional, Carr, John Jeffrey, additional, Koethe, John R., additional, and Wanjalla, Celestine N., additional

Published
2022
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5. Relationship of Subcutaneous Adipose Tissue Inflammation-related Gene Expression with Ectopic Lipid Deposition in Persons with HIV

Author

Bailin, Samuel S., primary, Gabriel, Curtis L., additional, Fan, Run, additional, Ye, Fei, additional, Nair, Sangeeta, additional, Terry, James G., additional, Carr, John Jeffrey, additional, Silver, Heidi, additional, Wanjalla, Celestine N., additional, Mashayekhi, Mona, additional, Lima, Morgan, additional, Woodward, Beverly, additional, Hannah, LaToya, additional, Fuseini, Hubaida, additional, Ferguson, Jane F., additional, Kropski, Jonathan A., additional, and Koethe, John R., additional

Published
2022
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6. Leptin Promotes Greater Ki67 Expression in CD4+ T Cells From Obese Compared to Lean Persons Living With HIV

Author

Fuseini, Hubaida, primary, Smith, Rita, additional, Nochowicz, Cindy H., additional, Simmons, Joshua D., additional, Hannah, LaToya, additional, Wanjalla, Celestine N., additional, Gabriel, Curtis L., additional, Mashayekhi, Mona, additional, Bailin, Samuel S., additional, Castilho, Jessica L., additional, Hasty, Alyssa H., additional, Koethe, John R., additional, and Kalams, Spyros A., additional

Published
2022
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7. GSK2256294 Decreases sEH (Soluble Epoxide Hydrolase) Activity in Plasma, Muscle, and Adipose and Reduces F2-Isoprostanes but Does Not Alter Insulin Sensitivity in Humans

Author

Luther, James M., primary, Ray, Justina, additional, Wei, Dawei, additional, Koethe, John R., additional, Hannah, Latoya, additional, DeMatteo, Anthony, additional, Manning, Robert, additional, Terker, Andrew S., additional, Peng, Dungeng, additional, Nian, Hui, additional, Yu, Chang, additional, Mashayekhi, Mona, additional, Gamboa, Jorge, additional, and Brown, Nancy J., additional

Published
2021
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8. Hepatic Steatosis and Ectopic Fat Are Associated With Differences in Subcutaneous Adipose Tissue Gene Expression in People With HIV

Author

Gabriel, Curtis L., primary, Ye, Fei, additional, Fan, Run, additional, Nair, Sangeeta, additional, Terry, James G., additional, Carr, John Jeffrey, additional, Silver, Heidi, additional, Baker, Paxton, additional, Hannah, LaToya, additional, Wanjalla, Celestine, additional, Mashayekhi, Mona, additional, Bailin, Sam, additional, Lima, Morgan, additional, Woodward, Beverly, additional, Izzy, Manhal, additional, Ferguson, Jane F., additional, and Koethe, John R., additional

Published
2021
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10. Leptin Promotes Greater Ki67 Expression in CD4 + T Cells From Obese Compared to Lean Persons Living With HIV.

Author

Fuseini H, Smith R, Nochowicz CH, Simmons JD, Hannah L, Wanjalla CN, Gabriel CL, Mashayekhi M, Bailin SS, Castilho JL, Hasty AH, Koethe JR, and Kalams SA

Subjects
Adult, Biomarkers, Body Mass Index, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes virology, Cytokines metabolism, Female, Flow Cytometry, HIV Infections virology, Humans, Ki-67 Antigen genetics, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Lymphocyte Activation, Lymphocyte Count, Male, Middle Aged, Obesity genetics, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes metabolism, Gene Expression, HIV Infections genetics, Ki-67 Antigen metabolism, Leptin pharmacology, Obesity metabolism
Abstract

While antiretroviral therapy (ART) has proven effective in suppressing viremia and disease progression among people living with human immunodeficiency virus (HIV; PLWH), suboptimal CD4 + T cell reconstitution remains a major obstacle in nearly 30% of ART-treated individuals. Epidemiological studies demonstrate that obesity, or a body mass index (BMI) ≥ 30 kg/m 2 , is positively correlated with greater CD4 + T cell recovery in PLWH on ART. Leptin is a known immunomodulator that is produced in proportion to fat mass and is increased in obese individuals, including PLWH. We hypothesized that CD4 + T cells from obese PLWH have increased cell proliferation and cytokine production compared to cells from lean PLWH, potentially modulated by differential effects of leptin signaling. To test this hypothesis, peripheral blood mononuclear cells from obese and lean PLWH with long-term virologic suppression on the same ART regimen were pretreated with recombinant leptin and then stimulated with anti-CD3/CD28 or PMA/ionomycin to measure Ki67 expression, leptin receptor (LepR) surface expression and cytokine production. In the absence of leptin, Ki67 expression and IL-17A production were significantly higher in CD4 + T cells from obese compared to lean PLWH. However, LepR expression was significantly lower on CD4 + T cells from obese compared to lean PLWH. After leptin treatment, Ki67 expression was significantly increased in CD4 + T cells from obese PLWH compared to the lean participants. Leptin also increased IL-17A production in CD4 + T cells from obese healthy controls. In contrast, leptin decreased IL-17A production in CD4 + T cells from both obese and lean PLWH. Combined, these results demonstrate that obesity is associated with greater CD4 + T cell proliferation among PLWH, and that higher circulating leptin levels in obesity may contribute to improved CD4 + T reconstitution in PLWH initiating ART., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fuseini, Smith, Nochowicz, Simmons, Hannah, Wanjalla, Gabriel, Mashayekhi, Bailin, Castilho, Hasty, Koethe and Kalams.)

Published
2022
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