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Brown Adipose Tissue Sheds Extracellular Vesicles That Carry Potential Biomarkers of Metabolic and Thermogenesis Activity Which Are Affected by High Fat Diet Intervention.

ABSTRACT: Brown adipose tissue (BAT) is a key target for the development of new therapies against obesity due to its role in promoting energy expenditure; BAT secretory capacity is emerging as an important contributor to systemic effects, in which BAT extracellular vesicles (EVs) (i.e., batosomes) might be protagonists. EVs have emerged as a relevant cellular communication system and carriers of disease biomarkers. Therefore, characterization of the protein cargo of batosomes might reveal their potential as biomarkers of the metabolic activity of BAT. In this study, we are the first to isolate batosomes from lean and obese Sprague-Dawley rats, and to establish reference proteome maps. An LC-SWATH/MS analysis was also performed for comparisons with EVs secreted by white adipose tissue (subcutaneous and visceral WAT), and it showed that 60% of proteins were exclusive to BAT EVs. Precisely, batosomes of lean animals contain proteins associated with mitochondria, lipid metabolism, the electron transport chain, and the beta-oxidation pathway, and their protein cargo profile is dramatically affected by high fat diet (HFD) intervention. Thus, in obesity, batosomes are enriched with proteins involved in signal transduction, cell communication, the immune response, inflammation, thermogenesis, and potential obesity biomarkers including UCP1, Glut1, MIF, and ceruloplasmin. In conclusion, the protein cargo of BAT EVs is affected by the metabolic status and contains potential biomarkers of thermogenesis activity.

SUBMITTER: Camino T

PROVIDER: S-EPMC9504916 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Brown Adipose Tissue Sheds Extracellular Vesicles That Carry Potential Biomarkers of Metabolic and Thermogenesis Activity Which Are Affected by High Fat Diet Intervention.

Camino Tamara T Lago-Baameiro Nerea N Sueiro Aurelio A Bravo Susana Belén SB Couto Iván I Santos Francisco Fernando FF Baltar Javier J Casanueva Felipe F FF Pardo María M

International journal of molecular sciences 20220916 18

Brown adipose tissue (BAT) is a key target for the development of new therapies against obesity due to its role in promoting energy expenditure; BAT secretory capacity is emerging as an important contributor to systemic effects, in which BAT extracellular vesicles (EVs) (i.e., batosomes) might be protagonists. EVs have emerged as a relevant cellular communication system and carriers of disease biomarkers. Therefore, characterization of the protein cargo of batosomes might reveal their potential ...[more]

PMID: 36142750

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Project description:BackgroundBrown adipose tissue (BAT) is considered as a primary location of adaptive thermogenesis and the thermogenic activities of brown adipocytes are also connected to generating heat and counteracting obesity. Recent studies revealed that BAT could secrete certain batokines-like factors especially small extracellular vesicles (sEVs), which contributed to the systemic consequences of BAT activities. As a newly emerging class of mediators, some long non-coding RNAs (lncRNAs) have exhibited metabolic regulatory effects in adipocyte development. However, besides the well-studied lncRNAs, the lncRNAs carried by sEVs derived from brown adipose tissue (sEV-BAT) have not been identified yet. RESULTS: In this study, we demonstrated that sEV-BAT could induce beige adipocyte differentiation both in ASCs and 3T3-L1 cells, while sEV-WAT had no corresponding effects. The lncRNA microarray assay on sEV-WAT and sEV-BAT revealed a total of 563 types of known lncRNAs were identified to be differentially expressed, among which 232 lncRNAs were upregulated and 331 lncRNAs were downregulated in sEV-BAT. Three novel candidates (AK029592, humanlincRNA1030 and ENSMUST00000152284) were selected for further validation. LncRNA-mRNA network analysis revealed candidate lncRNAs were largely embedded in cellular metabolic pathways. During adipogenic and thermogenic phenotype differentiation in ASCs and 3T3-L1 cells, only the expressions of AK029592 were upregulated. The three lncRNAs were all relatively enriched in brown adipose tissues and brown adipocytes. In different adipocytes, sEV and adipose tissue, the expression of AK029592 and ENSMUST00000152284 were remarkably decreased in obese mice compared to lean mice, while obesity state could not change the expression of humanlincRNA1030.ConclusionCollectively, our profiling study provided a comprehensive catalog for the study of lncRNAs specifically carried by sEV-BAT and indicated the potential regulatory role of certain sEV-BAT lncRNAs in thermogenesis.

Dataset Information

Brown Adipose Tissue Sheds Extracellular Vesicles That Carry Potential Biomarkers of Metabolic and Thermogenesis Activity Which Are Affected by High Fat Diet Intervention.

Publications

Brown Adipose Tissue Sheds Extracellular Vesicles That Carry Potential Biomarkers of Metabolic and Thermogenesis Activity Which Are Affected by High Fat Diet Intervention.

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