Exosomal proteins constitute an essential part of the human adipose tissue secretome

Hartwig, Sonja; Filippo, Elisabetta De; Göddeke, Simon; Knebel, Birgit; Kotzka, Jörg; Al-Hasani, Hadi; Roden, Michael; Sell, Henrike

doi:10.1016/j.bbapap.2018.11.009

Cited by 75 publications

(72 citation statements)

References 50 publications

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“…To our knowledge, this is the first study analyzing the C3H10T1/2 adipocytes-derived EVs; moreover, the present manuscript shows novel results by identifying protein cargo changes on EVs from the same cells after lipid hypertrophy or under insulin resistance by qualitative and quantitative (SWATH) label free mass spectrometry analysis. Previous EVs proteomics analysis were published using 3T3-L1 and 3T3-F442A adipocyte murine cell lines [16,17], and also from human primary SAT adipocytes in culture of two lean to moderate obese patients [44] whose results were indeed compared to ours herein; however, none of the previous proteomics analysis described vesicle protein cargo under metabolic insults as far we are aware.…”

Section: Despite the Recent Up Surge Of Extracellular Vesicles Revealsupporting

confidence: 61%

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

Camino

Lago-Baameiro

Bravo

et al. 2020

IJMS

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Extracellular vesicles (EVs) have recently emerged as a relevant way of cell to cell communication, and its analysis has become an indirect approach to assess the cell/tissue of origin status. However, the knowledge about their nature and role on metabolic diseases is still very scarce. We have established an insulin resistant (IR) and two lipid (palmitic/oleic) hypertrophied adipocyte cell models to isolate EVs to perform a protein cargo qualitative and quantitative Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) analysis by mass spectrometry. Our results show a high proportion of obesity and IR-related proteins in pathological EVs; thus, we propose a panel of potential obese adipose tissue EV-biomarkers. Among those, lipid hypertrophied vesicles are characterized by ceruloplasmin, mimecan, and perilipin 1 adipokines, and those from the IR by the striking presence of the adiposity and IR related transforming growth factor-beta-induced protein ig-h3 (TFGBI). Interestingly, functional assays show that IR and hypertrophied adipocytes induce differentiation/hypertrophy and IR in healthy adipocytes through secreted EVs. Finally, we demonstrate that lipid atrophied adipocytes shed EVs promote macrophage inflammation by stimulating IL-6 and TNFα expression. Thus, we conclude that pathological adipocytes release vesicles containing representative protein cargo of the cell of origin that are able to induce metabolic alterations on healthy cells probably exacerbating the disease once established.

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Section: Despite the Recent Up Surge Of Extracellular Vesicles Revealsupporting

confidence: 61%

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

Camino

Lago-Baameiro

Bravo

et al. 2020

IJMS

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“…Literature on secreted proteins from adipocytes or adipose tissue was searched online and in total 24 research papers and five reviews were found (Table 1) [2,3,8,16,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42]. Comparing our secretome data set with the data reported in these papers, 49 secreted proteins were identified as novel secreted proteins that had not been described before for adipocytes or adipose tissue (Table 2).…”

Section: Resultsmentioning

confidence: 99%

Glucose Restriction Plus Refeeding in Vitro Induce Changes of the Human Adipocyte Secretome with an Impact on Complement Factors and Cathepsins

Qiao

Bouwman

Baak

et al. 2019

IJMS

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Adipose tissue is a major endocrine organ capable of secreting adipokines with a role in whole-body metabolism. Changes in the secretome profile during the development of obesity is suspected to contribute to the risk of health complications such as those associated with weight regain after weight loss. However, the number of studies on weight regain is limited and secretome changes during weight regain have hardly been investigated. In an attempt to generate leads for in vivo studies, we have subjected human Simpson Golabi Behmel Syndrome adipocytes to glucose restriction (GR) followed by refeeding (RF) as an in vitro surrogate for weight regain after weight loss. Using LC-MS/MS, we compared the secreted protein profile after GR plus RF with that of normal feeding (NF) to assess the consequences of GR plus RF. We identified 338 secreted proteins of which 49 were described for the first time as being secreted by adipocytes. In addition, comparison between NF and GR plus RF showed 39 differentially secreted proteins. Functional classification revealed GR plus RF-induced changes of enzymes for extracellular matrix modification, complement system factors, cathepsins, and several proteins related to Alzheimer’s disease. These observations can be used as clues to investigate metabolic consequences of weight regain, weight cycling or intermittent fasting.

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“…Their paracrine activity suggested an inhibition of fibrosis [60]. In fact, ASCs release paracrine factor RNAs and extracellular proteins, including cytokines and growth factors, which promote healing and show therapeutic effects [61,62]. Moreover, ASCs also produce antioxidants, chaperone proteins, angiogenic, and antiapoptotic factors [1,6].…”

Section: Other Applicationsmentioning

confidence: 99%

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

Jankowski

Dompe

Sibiak

et al. 2020

Cells

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Adipose-derived stem cells (ASCs) exhibiting mesenchymal stem cell (MSC) characteristics, have been extensively studied in recent years. Because they have been shown to differentiate into lineages such as osteogenic, chondrogenic, neurogenic or myogenic, the focus of most of the current research concerns either their potential to replace bone marrow as a readily available and abundant source of MSCs, or to employ them in regenerative and reconstructive medicine. There is close to consensus regarding the methodology used for ASC isolation and culture, whereas a number of molecular analyses implicates them in potential therapies of a number of pathologies. When it comes to clinical application, there is a range of examples of animal trials and clinical studies employing ASCs, further emphasizing the advancement of studies leading to their more widespread use. Nevertheless, in vitro studies will most likely continue to play a significant role in ASC studies, both providing the molecular knowledge of their ex vivo properties and possibly serving as an important step in purification and application of those cells in a clinical setting. Therefore, it is important to consider current methods of ASC isolation, culture, and processing. Furthermore, molecular analyses and cell surface properties of ASCs are essential for animal studies, clinical studies, and therapeutic applications of the MSC properties.

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Exosomal proteins constitute an essential part of the human adipose tissue secretome

Cited by 75 publications

References 50 publications

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

Glucose Restriction Plus Refeeding in Vitro Induce Changes of the Human Adipocyte Secretome with an Impact on Complement Factors and Cathepsins

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

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