307-OR: Defective G-CSF in the Secretome of Epicardial Adipose Cells Favors Apoptosis and Cellular Stress of Cardiac Progenitor Cells in Human Obesity

• Published in: Diabetes (New York, N.Y.) Vol. 73; p. 1
• Main Authors: Palma, Giuseppe, Caccioppoli, Cristina, Doria, Rossella, Genchi, Valentina Annamaria, Calderoni, Isabella, Bottio, Tomaso, Santarpino, Giuseppe, Cignarelli, Angelo, Natalicchio, Annalisa, Laviola, Luigi, Pezzolla, Angela, Valverde, Angela M, Milano, Aldo D, Giorgino, Francesco, Perrini, Sebastio
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01-06-2024
• Subjects: Actin; Adipocytes; Apoptosis; Bone growth; c-Jun protein; Cellular stress response; Colony-stimulating factor; Cytokines; Filaments; Granulocyte colony-stimulating factor; Heart; Inflammation; Leukocytes (granulocytic); Obesity; Phosphorylation; Progenitor cells; RANTES; Regeneration; Secretome; Stem cells; Transcription factors
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db24-307-OR

Introduction and Objective: Granulocyte colony-stimulating factor (G-CSF) was reported to induce myocardial regeneration by promoting mobilization of bone marrow stem cells to the injured heart; however, the beneficial effects of G-CSF are not fully understood. We investigated the potential protective role of G-CSF in human cardiac progenitor cells (hCPC) exposed to the secretome from abdominal visceral (AV) and epicardial (E) adipose stem cells (ASC) and AV mature adipocytes from obese (Ob) subjects. Methods: AV ASC and mature adipocytes were isolated from 13 non-Obese (n-Ob) and 27 Ob patients. E ASC were isolated from 10 n-Ob and 9 Ob subjects. hCPC were isolated from n-Ob subjects undergoing elective cardiac surgery. Results: The secretome of AV and E adipose cells from Ob compared to n-Ob subjects displayed a different pattern of pro-inflammatory and anti-inflammatory cytokines: the levels of RANTES, MIP1B and IFN- γ were increased in Ob vs n-Ob subjects and showed a direct correlation with BMI (p<0.05); in contrast, the levels of G-CSF were markedly decreased particularly in the secretome of E-ASC from Ob compared to n-Ob subjects (p<0.05) and inversely correlated with BMI (p<0.05). Exposure of the hCPC to the adipose cell secretome from Ob, but not from n-Ob subjects, resulted in increased apoptosis and c-Jun phosphorylation, and impairment of actin filaments. Importantly, these effects were not observed when hCPC were pretreated with G-CSF. Conclusions: in human obesity, the secretome of AV and E ASC and mature adipocytes is enriched in pro-inflammatory cytokines that induce stress kinase activation and apoptosis in the hCPC. The ability to secrete G-CSF is specifically impaired in E ASC from Ob subjects. Since G-CSF can prevent the hCPC damage induced by pro-inflammatory cytokines from the Ob cell secretome, defective G-CSF in E ASC may represent a new pathogenetic mechanism that favors myocardial cell damage in human obesity.