Biology subjects

Noria, S.

Publications and source records attributed to Noria, S..

2 recordsLinked to original sources

bioRxiv2025

Human differentiated adipocytes can serve as surrogate mature adipocytes for adipocyte-derived extracellular vesicle analysis

Obesity is a growing global health concern, contributing to diseases such as cancer, autoimmune disorders, and neurodegenerative conditions. Adipose tissue dysfunction, characterized by abnormal adipokine secretion and chronic inflammation, plays a key role in these conditions. Adipose-derived extracellular vesicles (ADEVs) have emerged as critical mediators in obesity-related diseases. However, the study of mature adipocyte-derived EVs (mAdipo-EVs) is limited due to the short lifespan of mature adipocytes in culture, low EV yields, and the low abundance of these EV subpopulations in the circulation. Additionally, most studies rely on rodent models, which have differences in adipose tissue biology compared to humans. To overcome these challenges, we developed a standardized approach for differentiating human preadipocytes (preAdipos) into mature differentiated adipocytes (difAdipos), which produce high-yield, human adipocyte EVs (Adipo-EVs). Using visceral adipose tissue from bariatric surgical patients, we isolated the stromal vascular fraction (SVF) and differentiated preAdipos into difAdipos. Brightfield microscopy revealed that difAdipos exhibited morphological characteristics comparable to mature adipocytes (mAdipos) directly isolated from visceral adipose tissue, confirming their structural similarity. Additionally, qPCR analysis demonstrated decreased preadipocyte markers and increased mature adipocyte markers, further validating successful differentiation. Functionally, difAdipos exhibited lipolytic activity comparable to mAdipos, supporting their functional resemblance to native adipocytes. We then isolated preAdipo-EVs and difAdipo-EVs using tangential flow filtration and characterized them using bulk and single EV analysis. DifAdipo-EVs displayed classical EV and adipocyte-specific markers, with significant differences in biomarker expression compared to preAdipo-EVs. These findings demonstrate that difAdipos serve as a reliable surrogate for mature adipocytes, offering a consistent and scalable source of adipocyte-derived EVs for studying obesity and its associated disorders.

cell biology↗

bioRxiv2024

Novel multiparametric bulk and single EV pipeline for adipose cell-specific biomarker discovery in paired human biospecimens

Obesity remains a growing and global public health burden across a broad spectrum of metabolic, systemic, and neurodegenerative diseases. Previously considered merely a fat storage depot, adipose tissue is now recognized as an active endocrine organ crucial for metabolic and systemic regulation of local and distant organs. A burgeoning line of investigation centers on adipose-derived extracellular vesicles (ADEVs) and their pivotal role in obesity-associated pathobiology. However, robust methodologies are lacking for specifically isolating and characterizing human ADEVs. To bridge this gap, we have developed a robust multiparametric framework incorporating bulk and single EV characterization, proteomics, and mRNA phenotyping. EVs from matched human visceral adipose tissue, mature adipocyte-conditioned media, and plasma collected from the same individual bariatric surgical patients were analyzed and subjected to bottom-up proteomics analysis. This framework integrates bulk EV proteomics for cell-specific marker identification and subsequent single EV interrogation with single-particle interferometric reflectance imaging (SP-IRIS) and total internal reflection fluorescence (TIRF) microscopy. Our proteomics analysis revealed 76 unique proteins from adipose tissue-derived EVs (ATEVs), 512 unique proteins from adipocyte EVs (aEVs), and 1003 shared proteins. Prominent pathways enriched in ATEVs included lipid metabolism, extracellular matrix organization, and immune modulation, while aEVs exhibited enhanced roles in chromatin remodeling, oxidative stress responses, and metabolic regulation. Notably, adipose tissue-specific proteins such as adiponectin and perilipin were highly enriched in ADEVs and confirmed in circulating plasma EVs. Colocalization of key EV and adipocyte markers, including CD63 and PPARG, were validated in circulating plasma EVs. In summary, our study paves the way toward a tissue and cell-specific, multiparametric framework for an adiposity EV signature in obesity-driven diseases.

molecular biology↗