title: Impaired adipogenesis and insulin resistance in epicardial fat-mesenchymal cells from patients with cardiovascular disease.
abstract: 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.
authors.affiliation: Health Research Institute, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Fernández-Trasancos
authors.forename: Rubén
authors.initials: R
authors.lastname: Fandiño-Vaquero
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Agra
authors.forename: Angel Luis
authors.initials: AL
authors.lastname: Fernández
authors.forename: Juan E
authors.initials: JE
authors.lastname: Viñuela
authors.forename: José Ramón
authors.initials: JR
authors.lastname: González-Juanatey
authors.forename: Sonia
authors.initials: S
authors.lastname: Eiras
mesh_terms: D050156:Adipogenesis; D000368:Aged; D001706:Biopsy; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology*; D054337:Cell Dedifferentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008648:Mesoderm / Q000473:pathology*; D010496:Pericardium / Q000473:pathology*; D010736:Phosphoglycerate Mutase / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D040901:Proteomics; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000473:pathology*
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; C495692:SLC2A4 protein, human; D011972:Receptor, Insulin; D010736:Phosphoglycerate Mutase; D005947:Glucose