BACKGROUND: Obesity, a growing health concern, often leads to metabolic disturbances, systemic inflammation, and vascular dysfunction. Emerging evidence suggests that adipose tissue-derived extracellular vesicles (adiposomes) may propagate obesity-related complications. However, their lipid composition and effect on cardiometabolic state remain unclear. METHODS: This study examined the lipid composition of adiposomes in 122 participants (75 in obesity group, 47 in lean group) and its connection to cardiometabolic risk. Adiposomes were isolated via ultracentrifugation and characterized using nanoparticle tracking and comprehensive lipidomic analysis by mass spectrometry. Cardiometabolic assessments included anthropometry, body composition, glucose-insulin homeostasis, lipid profiles, inflammatory markers, and vascular function. RESULTS: Compared with lean controls, individuals with obesity exhibited elevated adiposome release and shifts in lipid composition, including higher ceramides, free fatty acids, and acylcarnitines, along with reduced levels of phospholipids and sphingomyelins. These alterations strongly correlated with increased BMI, insulin resistance, systemic inflammation, and impaired vascular function. Pathway enrichment analyses highlight dysregulation in glycerophospholipid and sphingolipid metabolism, bile secretion, proinflammatory pathways, and vascular contractility. Machine-learning models utilizing adiposome lipid data accurately classified obesity and predicted cardiometabolic conditions, such as diabetes, hypertension, dyslipidemia, and liver steatosis, achieving accuracy above 85%. CONCLUSION: Obesity profoundly remodels the adiposome lipid landscape, linking lipid changes to inflammation, metabolic dysfunction, and vascular impairment. These findings underscore adiposome lipids as biomarkers for obesity and related cardiometabolic disorders, supporting personalized interventions and offering therapeutic value in risk stratification and treatment. FUNDING: This project was supported by NIH grants R01HL161386, R00HL140049, P30DK020595 (PI: AMM), R01DK104927, and P30DK020595 as well as by a VA Merit Award (1I01BX003382, PI: BTL).

Breast cancer has become the most common cancer in the US and worldwide. While advances in early detection and treatment have resulted in a 40% reduction in breast cancer mortality, this reduction has not been achieved uniformly among racial groups. A large percentage of non-metastatic breast cancer mortality is related to the cardiovascular effects of breast cancer therapies. These effects appear to be more prevalent among patients from historically marginalized racial/ethnic backgrounds, such as African American and Hispanic individuals. Anthracyclines, particularly doxorubicin and daunorubicin, are the first-line treatments for breast cancer patients. However, their use is limited by their dose-dependent and cumulative cardiotoxicity, manifested by cardiomyopathy, ischemic heart disease, arrhythmias, hypertension, thromboembolic disorders, and heart failure. Cardiotoxicity risk factors, such as genetic predisposition and preexisting obesity, diabetes, hypertension, and heart diseases, are more prevalent in racial/ethnic minorities and undoubtedly contribute to the risk. Yet, beyond these risk factors, racial/ethnic minorities also face unique challenges that contribute to disparities in the emerging field of cardio-oncology, including socioeconomic factors, food insecurity, and the inability to access healthcare providers, among others. The current review will address genetic, clinical, and social determinants that potentially contribute to this disparity.

Our recent findings revealed that human adipose tissues (AT)-derived extracellular vesicles (adiposomes) vary in cargo among obese and lean individuals. The main objective of this study was to investigate the adiposomal lipid profiles and their correlation with cardiometabolic risk factors. AT samples were collected from obese subjects and lean controls and analyzed for their characteristics and lipid content. In addition, we measured the correlation between adiposomal lipid profiles and body composition, glucose and lipid metabolic profiles, brachial artery vasoreactivity, AT arteriolar flow-induced dilation, and circulating markers such as IL-6, C-reactive protein, and nitric oxide (NO). Compared to lean controls, adiposomes isolated from obese subjects were higher in number after normalization to AT volume. The two major lipid classes differentially expressed were lysophosphatidylcholine/phosphatidylcholine (LPC/PC) and ceramides (Cer). All lipids in the LPC/PC class were several-fold lower in adiposomes from obese subjects compared to lean controls, on top of which were PC 18:2, PC 18:1, and PC 36:3. Most ceramides were markedly upregulated in the obese group, especially Cer d37:0, Cer d18:0, and Cer d39:0. Regression analyses revealed associations between adiposomal lipid profiles and several cardiometabolic risk factors such as body mass index (BMI), fat percentage, insulin resistance, arteriolar and brachial artery vasoreactivity, NO bioavailability, and high-density lipoproteins (HDL-C). We conclude that the ability of adiposomes from obese subjects to disrupt cardiometabolic function could be partly attributed to the dysregulated lipid cargo.

Background: Adipose-derived extracellular vesicles (adiposomes) are emerging as key mediators of inter-organ communication, yet their molecular composition and role in obesity-related pathophysiology remain underexplored. This study integrates clinical phenotyping with proteomic analysis of visceral adipose-derived adiposomes to identify obesity-linked molecular disruptions. Methods: Seventy-five obese and forty-seven lean adults were extensively profiled for metabolic, inflammatory, hepatic, and vascular parameters. Adiposomes isolated from visceral fat underwent mass spectrometry-based proteomic analysis, followed by differential abundance, pathway enrichment, regulatory network modeling, and clinical association testing. Results: Obese individuals exhibited widespread cardiometabolic dysfunction. Proteomics revealed 64 adiposomal proteins with differential abundance. Upregulated proteins (e.g., CRP, C9, APOC1) correlated with visceral adiposity, systemic inflammation, and endothelial dysfunction. In contrast, downregulated proteins (e.g., ADIPOQ, APOD, TTR, FGB, FGG) were associated with enhanced nitric oxide bioavailability and vascular protection, suggesting loss of homeostatic signaling. Network analyses identified TNF and IL1 as key upstream regulators driving inflammatory and oxidative stress pathways. Decision tree and random forest models accurately classified obesity, hypertension, diabetes, dyslipidemia, and hepatic steatosis (AUC = 0.908–0.994), identifying predictive protein signatures related to complement activation, inflammation, and lipid transport. Conclusion: Obesity alters adiposome proteomic cargo, reflecting and potentially mediating systemic inflammation, metabolic dysregulation, and vascular impairment.

Adipose tissue-derived extracellular vesicles (adiposomes) carry a protein cargo that we previously showed differs between obese and lean individuals. In this study, we investigate how adiposomal protein cargo changes in response to sleeve gastrectomy and examine whether these changes are associated with clinical improvements. Twenty-three obese adults underwent pre- and post-bariatric surgery adipose sampling for adiposome isolation and clinical assessments that included vascular and metabolic profiles and inflammatory markers. The adiposomal protein cargo was analyzed via non-targeted proteomics. Differential protein abundance, pathway enrichment, and correlation analyses were assessed. Twelve weeks after bariatric surgery, BMI and fat mass decreased, accompanied by improved glucose and lipid profiles. Inflammatory markers (leptin, IL-6, CRP) also declined, while adiponectin and nitric oxide increased. Adiposomal proteomics identified 287 proteins, with 138 significantly altered. Downregulated proteins included PRDX2, FN1, SERPIND1, and inflammatory mediators; upregulated proteins included talin-1, fibrinogens, and adiponectin. Correlation analysis linked these changes to improvements in lipid profiles, vascular function, and circulating inflammatory markers. Pathway analysis revealed inhibition of lipid-regulatory pathways alongside enrichment of immune, metabolic, and vascular pathways, including lipoprotein metabolism and endothelial signaling. Bariatric surgery-induced cardiometabolic improvements were accompanied by adiposome proteomic remodeling, characterized by reduced inflammation and metabolic reprogramming.

Background: Prior studies established adipose‐derived extracellular vesicles, or adiposomes, as mediators of interorgan communication with lipidomic signatures linked to cardiometabolic health. Because adiposomes signal to distant organs via the circulation, we examined whether circulating adiposome lipidomes reflect matched subcutaneous adipose tissue adiposomes. Methods: This cross‐sectional paired lipidomic study included 22 subjects with matched circulating and subcutaneous adipose tissue adiposome samples. Untargeted lipidomics quantified 773 lipid features across 18 detected broad classes. Spearman correlation was the primary across‐subject species‐level metric; pooled and within‐subject Pearson and Spearman correlations, principal component analysis, Bland–Altman analysis, class composition, and matched‐versus‐mismatched similarity were complementary measures. Additional analyses evaluated sex, cardiometabolic phenotypes, and focused species‐clinical associations. Results: Across 770 species with valid across‐subject estimates, the median plasma‐subcutaneous Spearman ρ was 0.101 and no species survived Benjamini‐Hochberg false‐discovery‐rate correction, although 553 (71.8%) correlations were positive. Mean broad‐class composition was highly conserved (Spearman ρ = 0.996; Pearson r on log ₂ percentages = 0.996). Matched whole‐profile similarity was not greater than mismatched similarity (median ρ = 0.818 vs. 0.811; p = 0.620), and the matched sample was the closest pair for 0 of 22 participants. Neither sex nor any prespecified cardiometabolic phenotype explained matched‐profile similarity after correction, and no focused species‐clinical association survived full‐screen FDR correction. Conclusions: Circulating and subcutaneous adiposome lipidomes share a highly conserved mean class architecture, but individual species, subject‐specific matching, and clinical‐association patterns are not interchangeable. Plasma adiposomes may therefore serve as complementary circulating readouts of adipose‐derived interorgan lipid signaling rather than direct tissue substitutes.