Adipose tissue is an active endocrine organ that can secrete a wide number of factors to regulate adipogenesis via paracrine signals. In addition to soluble proteins in adipose tissue, microRNAs (miRNAs) enriched in extracellular vesicles (EVs), such as exosomes or microvesicles, could modulate intercellular communications. In this study, we demonstrated that exosome-like vesicles derived from adipose tissue (Exo-AT) were internalized by adipose tissue-derived stem cells (ADSCs), and that these, in turn, induced adipogenesis. High-throughput sequencing showed that 45 miRNAs were enriched in Exo-AT, and 31.11% of them were associated with adipogenesis, compared with ADSC-derived exosome-like vesicles (Exo-ADSC). miR-450a-5p, one of the most abundant miRNAs in Exo-AT, was a proadipogenic miRNA. Further study demonstrated that miR-450a-5p promoted adipogenesis through repressing expression of WISP2 by targeting its 3′ untranslated region. Additionally, Exo-AT could also downregulate the expression of WISP2, while miR-450a-5p inhibitor reversed this effect. Moreover, inhibition of miR-450a-5p impaired adipogenesis mediated by exosome-like vesicles. In conclusion, Exo-AT mediates adipogenic differentiation through a mechanism involving transfer of miR-450a-5p.

Introduction: Adipose tissue-derived extracellular vesicles (EVs-AT) are recognized as critical mediators of metabolic alterations in obesity-related diseases. However, few studies have focused on the role of lipids within EVs-AT in the development of obesity-related diseases.Methods: In this study, we performed a targeted lipidomic analysis to compare the lipidome of EVs secreted by inguinal white adipose tissue (EVs-iWAT), epididymal white adipose tissue (EVs-eWAT), and interscapular brown adipose tissue (EVs-BAT) in lean and obese mice.Results: We uncovered a comprehensive lipidomic map, revealing the diversity and specific lipid sorting in EVs-iWAT, EVs-eWAT, and EVs-BAT in obesity. Biological function analyses suggested that lipids encapsulated within EVs-AT of obese individuals might correlate with metabolism, pro-inflammatory response, and insulin resistance. These effects were particularly pronounced in EVs-eWAT and EVs-BAT.Conclusion: Our findings indicated that EVs-AT serves as novel carriers for lipokines, thereby mediating the biological functions of EVs-AT. This study holds promise for the identification of new biomarkers for obesity-related diseases and the development of new strategies to combat metabolic diseases.