Exploring visceral and subcutaneous adipose tissue secretomes in human obesity: implications for metabolic disease
Open accessAbstract
Adipose tissue secretions are depot-specific and vary based on anatomical location. Considerable attention has been focused on visceral (VAT) and subcutaneous (SAT) adipose tissue with regard to metabolic disease, yet our knowledge of the secretome from these depots is incomplete. We conducted a comprehensive analysis of VAT and SAT secretomes in the context of metabolic function. Conditioned media generated using SAT and VAT explants from individuals with obesity were analyzed using proteomics, mass spectrometry, and multiplex assays. Conditioned media were administered in vitro to rat hepatocytes and myotubes to assess the functional impact of adipose tissue signaling on insulin responsiveness. VAT secreted more cytokines (IL-12p70, IL-13, TNF-α, IL-6, and IL-8), adipokines (matrix metalloproteinase-1, PAI-1), and prostanoids (TBX2, PGE2) compared with SAT. Secretome proteomics revealed differences in immune/inflammatory response and extracellular matrix components. In vitro, VAT-conditioned media decreased hepatocyte and myotube insulin sensitivity, hepatocyte glucose handling, and increased basal activation of inflammatory signaling in myotubes compared with SAT. Depot-specific differences in adipose tissue secretome composition alter paracrine and endocrine signaling. The unique secretome of VAT has distinct and negative impact on hepatocyte and muscle insulin action.
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Adipose depot location greatly influences metabolic health.
“The WAT secretome is composed of cytokines, adipokines, and other factors, which can be reviewed here (12), and adipose depot location greatly influences metabolic health (13, 14).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [13]
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- Authors
- Kahn, D., Macias, E., Zarini, S., Garfield, A., Zemski Berry, K., MacLean, P., Gerszten, R. E., Libby, A., Solt, C., Schoen, J., & Bergman, B. C.
- Affiliations
- University of Colorado Anschutz (US)
- Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 , USA
- Harvard University (US)
- Corresponding author
- Bergman, Bryan C
- ORCID
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2022-08-29
- Volume
- 163
- Issue
- 11
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC9761573
- OpenAlex
- W4293761227
- Cited by
- 97
- References
- 58
- Citations by year
- 2026: 33 · 2025: 28 · 2024: 23 · 2023: 12 · 2022: 1
- FWCI
- 11.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Endocrinology (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health General Clinical Research Center (RR-00036)
- NIDDK (R01DK118149, F31DK126393)
- Colorado Nutrition Obesity Research Center (P30DK048520)
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- visceral adipose tissue, subcutaneous adipose tissue, adipose tissue secretome, obesity, metabolic disorders, insulin sensitivity, hepatocytes, myotubes, cytokines, adipokines, prostanoids, paracrine signaling, hormone signaling, inflammation, extracellular matrix, conditioned medium
- MeSH terms
- Isophane Insulin, Human, Secretome, Animals, Glucose, Humans, Insulin Resistance, Obesity, Tumor Necrosis Factor-alpha, Dinoprostone, Interleukin-6, Interleukin-8, Culture Media, Conditioned, Plasminogen Activator Inhibitor 1, Interleukin-13, Matrix Metalloproteinase 1, Subcutaneous Fat, Intra-Abdominal Fat, Rats, Adipokines
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