Quantifying the inflammatory secretome of human intermuscular adipose tissue
Abstract Adipose tissue secretes an abundance of lipid and protein mediators, and this secretome is depot‐specific, with local and systemic effects on metabolic regulation. Intermuscular adipose tissue (IMAT) accumulates within the skeletal muscle compartment in obesity, and is associated with insul...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-08-01
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| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.15424 |
| _version_ | 1811282456707334144 |
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| author | Darcy Kahn Emily Macias Simona Zarini Amanda Garfield Karin Zemski Berry Robert Gerszten Jonathan Schoen Melanie Cree‐Green Bryan C. Bergman |
| author_facet | Darcy Kahn Emily Macias Simona Zarini Amanda Garfield Karin Zemski Berry Robert Gerszten Jonathan Schoen Melanie Cree‐Green Bryan C. Bergman |
| author_sort | Darcy Kahn |
| collection | DOAJ |
| description | Abstract Adipose tissue secretes an abundance of lipid and protein mediators, and this secretome is depot‐specific, with local and systemic effects on metabolic regulation. Intermuscular adipose tissue (IMAT) accumulates within the skeletal muscle compartment in obesity, and is associated with insulin resistance and metabolic disease. While the human IMAT secretome decreases insulin sensitivity in vitro, its composition is entirely unknown. The current study was conducted to investigate the composition of the human IMAT secretome, compared to that of the subcutaneous (SAT) and visceral adipose tissue (VAT) depots. IMAT, SAT, and VAT explants from individuals with obesity were used to generate conditioned media. Proteomics analysis of conditioned media was performed using multiplex proximity extension assays, and eicosanoid analysis using liquid chromatography–tandem mass spectrometry. Compared to SAT and/or VAT, IMAT secreted significantly more cytokines (IL2, IL5, IL10, IL13, IL27, FGF23, IFNγ and CSF1) and chemokines (MCP1, IL8, CCL11, CCL20, CCL25 and CCL27). Adipokines hepatocyte growth factor and resistin were secreted significantly more by IMAT than SAT or VAT. IMAT secreted significantly more eicosanoids (PGE2, TXB2, 5‐HETE, and 12‐HETE) compared to SAT and/or VAT. In the context of obesity, IMAT is a distinct adipose tissue with a highly immunogenic and inflammatory secretome, and given its proximity to skeletal muscle, may be critical to glucose regulation and insulin resistance. |
| first_indexed | 2024-04-13T01:51:50Z |
| format | Article |
| id | doaj.art-89282c4a12b145a2b6743455e1dbda1e |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-04-13T01:51:50Z |
| publishDate | 2022-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-89282c4a12b145a2b6743455e1dbda1e2022-12-22T03:07:51ZengWileyPhysiological Reports2051-817X2022-08-011016n/an/a10.14814/phy2.15424Quantifying the inflammatory secretome of human intermuscular adipose tissueDarcy Kahn0Emily Macias1Simona Zarini2Amanda Garfield3Karin Zemski Berry4Robert Gerszten5Jonathan Schoen6Melanie Cree‐Green7Bryan C. Bergman8Division of Endocrinology, Diabetes, and Metabolism University of Colorado Anschutz Medical Campus Aurora Colorado USADivision of Endocrinology, Diabetes, and Metabolism University of Colorado Anschutz Medical Campus Aurora Colorado USADivision of Endocrinology, Diabetes, and Metabolism University of Colorado Anschutz Medical Campus Aurora Colorado USADivision of Endocrinology, Diabetes, and Metabolism University of Colorado Anschutz Medical Campus Aurora Colorado USADivision of Endocrinology, Diabetes, and Metabolism University of Colorado Anschutz Medical Campus Aurora Colorado USAThe Cardiovascular Research Center and Cardiology Division Massachusetts General Hospital, Harvard Medical School Boston USADepartment of Surgery University of Colorado Anschutz Medical Campus Aurora Colorado USADivision of Pediatric Endocrinology University of Colorado Anschutz Medical Campus Aurora Colorado USADivision of Endocrinology, Diabetes, and Metabolism University of Colorado Anschutz Medical Campus Aurora Colorado USAAbstract Adipose tissue secretes an abundance of lipid and protein mediators, and this secretome is depot‐specific, with local and systemic effects on metabolic regulation. Intermuscular adipose tissue (IMAT) accumulates within the skeletal muscle compartment in obesity, and is associated with insulin resistance and metabolic disease. While the human IMAT secretome decreases insulin sensitivity in vitro, its composition is entirely unknown. The current study was conducted to investigate the composition of the human IMAT secretome, compared to that of the subcutaneous (SAT) and visceral adipose tissue (VAT) depots. IMAT, SAT, and VAT explants from individuals with obesity were used to generate conditioned media. Proteomics analysis of conditioned media was performed using multiplex proximity extension assays, and eicosanoid analysis using liquid chromatography–tandem mass spectrometry. Compared to SAT and/or VAT, IMAT secreted significantly more cytokines (IL2, IL5, IL10, IL13, IL27, FGF23, IFNγ and CSF1) and chemokines (MCP1, IL8, CCL11, CCL20, CCL25 and CCL27). Adipokines hepatocyte growth factor and resistin were secreted significantly more by IMAT than SAT or VAT. IMAT secreted significantly more eicosanoids (PGE2, TXB2, 5‐HETE, and 12‐HETE) compared to SAT and/or VAT. In the context of obesity, IMAT is a distinct adipose tissue with a highly immunogenic and inflammatory secretome, and given its proximity to skeletal muscle, may be critical to glucose regulation and insulin resistance.https://doi.org/10.14814/phy2.15424conditioned mediaIMATinflammationinsulin sensitivityparacrine signaling |
| spellingShingle | Darcy Kahn Emily Macias Simona Zarini Amanda Garfield Karin Zemski Berry Robert Gerszten Jonathan Schoen Melanie Cree‐Green Bryan C. Bergman Quantifying the inflammatory secretome of human intermuscular adipose tissue Physiological Reports conditioned media IMAT inflammation insulin sensitivity paracrine signaling |
| title | Quantifying the inflammatory secretome of human intermuscular adipose tissue |
| title_full | Quantifying the inflammatory secretome of human intermuscular adipose tissue |
| title_fullStr | Quantifying the inflammatory secretome of human intermuscular adipose tissue |
| title_full_unstemmed | Quantifying the inflammatory secretome of human intermuscular adipose tissue |
| title_short | Quantifying the inflammatory secretome of human intermuscular adipose tissue |
| title_sort | quantifying the inflammatory secretome of human intermuscular adipose tissue |
| topic | conditioned media IMAT inflammation insulin sensitivity paracrine signaling |
| url | https://doi.org/10.14814/phy2.15424 |
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