Cited by 97Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

Exploring visceral and subcutaneous adipose tissue secretomes in human obesity: implications for metabolic disease

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Kahn, Darcy, Macias, Emily, Zarini, Simona, Garfield, Amanda, Zemski Berry, Karin, MacLean, Paul, Gerszten, Robert E, Libby, Andrew +3 more·2022·Endocrinology

Abstract

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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  1. Seglen PO. Preparation of isolated rat liver cells. Methods Cell Biol. 1976;13:29-83.

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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
Venue
Endocrinology
Published
2022-08-29
Volume
163
Issue
11
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
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
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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