Single-Cell Analysis of Subcutaneous Fat Reveals Profibrotic Cells That Correlate With Visceral Adiposity in HIV.

Context: Cardiometabolic diseases are common in persons with HIV (PWH) on antiretroviral therapy (ART), which has been attributed to preferential lipid storage in visceral adipose tissue (VAT) compared with subcutaneous adipose tissue (SAT). However, the relationship of SAT-specific cellular and molecular programs with VAT volume is poorly understood in PWH.

Objective: We characterized SAT cell-type specific composition and transcriptional programs that are associated with greater VAT volume in PWH on contemporary ART.

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

Introduction: 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.

Methods: We generated a comprehensive single-cell multi-omic SAT atlas to characterize cellular compositional and transcriptional changes in 59 PWH across a spectrum of metabolic health.

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

Background Persons with HIV have a higher prevalence of coronary artery disease compared with their HIV-negative counterparts. Earlier identification of subclinical atherosclerosis may provide a greater opportunity for cardiovascular disease risk reduction. We investigated coronary cross-sectional area (CorCSA) by noncontrasted computed tomography imaging as a noninvasive measure of arterial remodeling among virally suppressed persons with HIV.

Relationship of Subcutaneous Adipose Tissue Inflammation-Related Gene Expression With Ectopic Lipid Deposition in Persons With HIV.

Objective: Fat redistribution from subcutaneous adipose tissue (SAT) to the abdominal viscera, pericardium, liver, and skeletal muscle contributes to the rising burden of cardiometabolic disease among persons with HIV (PWH). Previous studies found SAT inflammation in PWH impairs lipid storage and persists despite plasma viral suppression on antiretroviral therapy (ART). In this study, we identified SAT immune-related genes associated with ectopic fat deposition in PWH on long-term ART.

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

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, 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.

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

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

Persons with human immunodeficiency virus (PWH) have subcutaneous adipose tissue (SAT) dysfunction related to antiretroviral therapy and direct viral effects, which may contribute to a higher risk of nonalcoholic fatty liver disease compared with human immunodeficiency virus-negative individuals. We assessed relationships between SAT expression of major adipocyte regulatory and lipid storage genes with hepatic and other ectopic lipid deposits in PWH. We enrolled 97 PWH on long-term antiretroviral therapy with suppressed plasma viremia and performed computed tomography measurements of liver attenuation, a measure of hepatic steatosis, skeletal muscle (SM) attenuation, and the volume of abdominal subcutaneous, visceral, and pericardial adipose tissue.

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.

Persons with HIV are at increased risk for diabetes mellitus compared with individuals without HIV. Adipose tissue is an important regulator of glucose and lipid metabolism, and adipose tissue T cells modulate local inflammatory responses and, by extension, adipocyte function. Persons with HIV and diabetes have a high proportion of CX3CR1 GPR56 CD57 (C-G-C) CD4 T cells in adipose tissue, a subset of which are cytomegalovirus specific, whereas individuals with diabetes but without HIV have predominantly CD69 CD4 T cells.