A Single-Cell Molecular Atlas of White Adipose Tissue Shows Differences in Myeloid and Lymphoid Cell Polarization in Type 2 Diabetes and HIV Infection

Subcutaneous white adipose tissue (scWAT) is a critical regulator of systemic metabolic homeostasis. HIV infection is accompanied by alterations in scWAT immune cells, which may contribute to the increased risk for cardiometabolic diseases in persons with HIV (PWH) and serve as a model to investigate cellular relationships. We generated the largest molecular atlas of scWAT in humans to date from 91 individuals using paired single-cell transcriptomic and proteogenomics to determine the scWAT immune profile in non-diabetic, pre-diabetic, and diabetic PWH, and HIV-negative diabetic persons. We identified a substantial increase in lipid-associated macrophages (LAMs) with glucose intolerance, and, in PWH only, CD4+ and CD8+ T effector memory cells were correlated with LAM proportion. Finally, we resolved adipogenic and fibrogenic cells at high resolution and found a strong association between LAMs and myofibroblasts. These results provide a high-resolution, multi-platform characterization of changes in scWAT composition that occur with metabolic disease and HIV. ### Competing Interest Statement J.A.K. consults for Boehringer Ingelheim, Janssen, and Bristol-Myers-Squibb, serves on the scientific advisory board for APIE Therapeutics, and provides non-financial study support to Genentech. J.R.K. has served as a consultant to Gilead Sciences, Merck, ViiV Healthcare, Theratechnologies, and Janssen, and has received research support from Gilead Sciences and Merck. C.N.W. serves on the scientific advisory board for ViiV Health Care.