1763-P: The Secretome from Visceral Adipose Stem Cells of Obese Subjects Induces Apoptosis and Insulin Resistance in Cardiac Progenitor Cells

Increased abdominal visceral adipose tissue (VAT) is associated with cardiovascular risk in metabolically unhealthy subjects. The viability of cardiac progenitor cells (CPC) is essential for myocardial tissue turnover. This study aimed to assess whether the secretome of visceral adipose stem cells (ASC) and ASC-derived mature adipocytes may affect the viability and insulin signaling of CPC in human obesity. ASC were isolated from VAT biopsies of nondiabetic subjects with varying levels of BMI and used before and after differentiation into adipocytes in vitro. CPC isolated from right auricle biopsies of healthy non-obese subjects were exposed or not to conditioned media (CM) of ASC or ASC-derived adipocytes. Apoptosis was assessed by caspase-3 cleavage and ELISA for oligonucleosomes, and insulin signaling by immunoblotting analysis of Akt Ser473 phosphorylation. The CM of ASC isolated from obese subjects (Ob-ASC) induced CPC apoptosis in a time-dependent manner (4-8-24 h) (p0.05 vs. control CPC). Similarly to Ob-ASC, exposure of CPC to the CM of ASC-derived adipocytes from obese subjects also induced apoptosis and inhibited insulin-mediated Akt phosphorylation (p0.05 vs. control CPC). In conclusion, human obesity is associated with the secretion of factors from visceral ASC that impair insulin action in CPC and CPC survival. This property is retained in ASC-derived adipocytes, providing a potential link between expansion of VAT and development of myocardial dysfunction. Disclosure S. Porro: None. S. Perrini: None. C. Caccioppoli: None. R. Doria: None. V. Genchi: None. A. Cignarelli: Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., Novo Nordisk A/S. A. Natalicchio: Other Relationship; Self; Novo Nordisk Inc., Sanofi-Aventis. L. Laviola: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc. Board Member; Self; AstraZeneca, Roche Diabetes Care, Sanofi-Aventis. Speaker's Bureau; Self; Medtronic, Mundipharma, Takeda Pharmaceutical Company Limited. F. Giorgino: Advisory Panel; Self; Aegerion Pharmaceuticals, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, MedImmune, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Roche Diabetes Care, Sanofi. Consultant; Self; Roche Diabetes Care, Sanofi. Research Support; Self; Eli Lilly and Company, LifeScan, Inc., Takeda Pharmaceutical Company Limited. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Sanofi.