Impaired Adipogenesis and Insulin Resistance in Epicardial Fat-Mesenchymal Cells From Patients With Cardiovascular Disease

• Published in: Journal of cellular physiology 2014-11, Vol.229 (11), p.1722-1730
• Main Authors: Fernández-Trasancos, Ángel, Fandiño-Vaquero, Rubén, Agra, Rosa María, Fernández, Ángel Luis, Viñuela, Juan E., González-Juanatey, José Ramón, Eiras, Sonia
• Format: Article
• Language: English
• Subjects: Adipogenesis; Adipose tissue; Aged; Biopsy; Cardiovascular diseases; Cardiovascular Diseases - metabolism; Cardiovascular Diseases - pathology; Cell Dedifferentiation - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Female; Glucose - metabolism; Glucose Transporter Type 4 - metabolism; Humans; Insulin - pharmacology; Insulin Resistance; Male; Mesoderm - pathology; Pericardium - pathology; Phosphoglycerate Mutase - metabolism; Protein Processing, Post-Translational - drug effects; Proteomics; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; Subcutaneous Fat - pathology
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.24619

The thickness of epicardial adipose tissue (EAT), which is an inflammatory source for coronary artery disease (CAD), correlates with insulin resistance. One trigger factor is impaired adipogenesis. Here, our aim was to clarify the underlying mechanisms of insulin resistance on EAT‐mesenchymal cells (MC). EAT and subcutaneous adipose tissue (SAT) were collected from 19 patients who were undergoing heart surgery. Their dedifferentiated adipocytes (DAs) and/or MCs were cultured. After the induction of adipogenesis or stimulation with insulin, the expression of adipokines was analyzed using real‐time polymerase chain reaction (PCR). Colorimetric assays were performed to measure glucose levels and proliferation rate. Proteins modifications were detected via the proteomic approach and Western blot. Our results showed lower adipogenic ability in EAT‐MCs than in SAT‐MCs. Maximum adiponectin levels were reached within 28–35 days of exposure to adipogenic inducers. Moreover, the adipogenesis profile in EAT‐MCs was dependent on the patients’ clinical characteristics. The low adipogenic ability of EAT‐MCs might be associated with an insulin‐resistant state because chronic insulin treatment reduced the inflammatory cytokine expression levels, improved the glucose consumption, and increased the post‐translational modifications (PTMs) of the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1). We found lower adipogenic ability in EAT‐MCs than in SAT‐MCs. This lower ability level was dependent on gender and the presence of diabetes, obesity, and CAD. Low adipogenesis ability and insulin resistance in EAT‐MCs might shed light on the association between EAT dysfunction and cardiovascular disease. J. Cell. Physiol. 229: 1722–1730, 2014. © 2014 Wiley Periodicals, Inc.