White Adipose Tissue Compositional and Transcriptional Patterns with Progressive Glucose Intolerance in Persons with HIV
Year: 2022
Type: preprint
Study design: Observational Study
Abstract: Subcutaneous adipose tissue (SAT) is a critical regulator of systemic metabolic homeostasis. Persons with HIV (PWH) have an increased risk of metabolic diseases and significant alterations in the SAT immune environment compared with the general population. We generated a comprehensive SAT atlas to characterize cellular compositional and transcriptional changes in 59 PWH with a spectrum of metabolic health. Glucose intolerance was associated with increased lipid-associated macrophages and CD4 + and CD8 + T effector memory cells, and decreased perivascular macrophages. We observed a coordinated intercellular regulatory program which enriched for genes related to inflammation and lipid-processing across multiple cell types as glucose intolerance increased. Increased CD4 + effector memory tissue resident cells most strongly associated with altered expression of adipocyte genes critical for lipid metabolism and cellular regulation. Many of these findings were present in a separate group of 32 diabetic HIV-negative persons, suggesting these changes are not specific to HIV.
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Vanderbilt University, Vanderbilt Institute for Clinical and Translational Research, National Institutes of Health, Center for AIDS Research, University of Washington, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G4038955393, G560889077, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, G7412434281, The Role of Adipose-Resident T Cells in HIV-Associated Glucose Intolerance, Tennessee Center for AIDS Research (TN-CFAR), Spatiotemporal genomic regulation of disease initiation and progression in pulmonary fibrosis, Institutional Career Development Core, Anti-cytomegalovirus Immune Responses in Atherosclerotic Cardiovascular Disease in Persons Living with HIV
OpenAlex ID: W4220730689