Giorgia Scichilone

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/Objectives: Bariatric surgery improves weight and metabolic health in individuals with severe obesity; however, challenges like gut dysbiosis and nutrient deficiencies persist postoperatively. Probiotic supplementation may enhance recovery by modulating gut microbiota. This updated meta-analysis aimed to assess the effects of probiotics/synbiotics on metabolic, anthropometric, and nutritional outcomes after bariatric surgery. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted using PubMed, SCOPUS, Web of Science, and CENTRAL through December 2024. Studies comparing probiotics/synbiotics (which contain both probiotics and prebiotics) versus a placebo in adults post-bariatric surgery were included. Meta-analyses were conducted, with subgroup analyses by surgery type, the timing of the intervention, and probiotic formulation (PROSPERO ID: CRD420251019199). Results: Thirteen RCTs involving 809 patients were included in the analysis. Probiotic use significantly reduced BMI (MD = 0.67, 95% CI: 0.33 to 1.00), HbA1c (MD = −0.19%, 95% CI: −0.36 to −0.01), triglycerides (MD = −16.56 mg/dL), and AST levels (MD = −3.68 U/L), while increasing ALP (MD = 8.12 U/L) and vitamin D (MD = 13.68 pg/mL). Ferritin levels were significantly lower (MD = −18.89 µg/L) in the probiotic group. A subgroup analysis showed enhanced benefits in patients undergoing mini-gastric bypass, with perioperative or synbiotic interventions specifically improving triglycerides, total cholesterol, and HbA1c. Conclusions: Probiotics may offer modest but significant improvements in BMI, glycemic control, lipid profile, liver enzymes, and vitamin D levels after bariatric surgery. These findings support the potential role of probiotics/synbiotics as an adjunct therapy, though further large-scale trials are warranted to confirm long-term benefits.

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).

Adipose tissue was previously regarded as a dormant organ for lipid storage until the identification of adiponectin and leptin in the early 1990s. This revelation unveiled the dynamic endocrine function of adipose tissue, which has expanded further. Adipose tissue has emerged in recent decades as a multifunctional organ that plays a significant role in energy metabolism and homeostasis. Currently, it is evident that adipose tissue primarily performs its function by secreting a diverse array of signaling molecules known as adipokines. Apart from their pivotal function in energy expenditure and metabolism regulation, these adipokines exert significant influence over a multitude of biological processes, including but not limited to inflammation, thermoregulation, immune response, vascular function, and insulin sensitivity. Adipokines are pivotal in regulating numerous biological processes within adipose tissue and facilitating communication between adipose tissue and various organs, including the brain, gut, pancreas, endothelial cells, liver, muscle, and more. Dysregulated adipokines have been implicated in several metabolic diseases, like obesity and diabetes, as well as cardiovascular diseases. In this article, we attempted to describe the significance of adipokines in developing metabolic and cardiovascular diseases and highlight their role in the crosstalk between adipose tissues and other tissues and organs.