Dysfunction of visceral and epicardial adipose tissue may alter heart performance and promote adverse cardiovascular outcomes in obesity and diabetes. We assessed whether the secretome from abdominal visceral (AV) and epicardial (E) adipose stem cells (ASC) and from AV mature adipocytes might affect the viability of human cardiac progenitor cells (hCPC) in human obesity, and the effects of dapagliflozin (DAPA) , a selective SGLT-2 inhibitor. ASC and mature adipocytes were isolated from AV and E adipose tissue biopsies of obese (Ob) and non-obese subjects, respectively. hCPC were isolated from right auricle biopsies of non-Ob, non-diabetic donors. hCPC were pretreated with uM DAPA for 24 h or left untreated, and then exposed to the conditioned media (CM) of AV-ASC, E-ASC, and AV mature adipocytes. The CM of AV-ASC, E-ASC, and AV mature adipocytes induced apoptosis, assessed by ELISA for cytoplasmic oligonucleosomes, in hCPC after 24 h (p<0.05) . Exposure of hCPC to the CM of AV-ASC, E-ASC, and AV mature adipocytes for 24 h also resulted in impaired organization of the hCPC actin filaments, assessed by indirect immunofluorescence (p<0.05) . In addition, the CM of AV-ASC, E-ASC, and AV mature adipocytes induced c-Jun phosphorylation, a measure of JNK activation, after 4 h and 8 h (p<0.05) . Importantly, these effects were not observed when the hCPC were exposed to the CM of AV-ASC, E-ASC, and AV mature adipocytes from non-Ob subjects. Pretreatment of hCPC with DAPA resulted in reduced apoptosis and less impairment of actin filaments following exposure to the CM of AV-ASC, E-ASC, and AV mature adipocytes (p<0.05) , as well as in reduced c-Jun phosphorylation (p<0.05) .

In conclusion, in human obesity, the secretome of both AV and E ASC and mature adipocytes induces stress kinase activation in hCPC and impairs their viability and functionality, and these effects can be counteracted by SGLT-2 inhibitors directly acting on the hCPC.


G.Palma: None. F.Giorgino: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Consultant; Lilly Diabetes, Sanofi, Research Support; Lilly Diabetes, Roche Diabetes Care, Takeda Pharmaceutical Company Limited. S.Perrini: None. C.Caccioppoli: None. R.Doria: None. V.Genchi: None. G.Santarpino: None. A.Cignarelli: None. A.Natalicchio: Consultant; Novo Nordisk, Other Relationship; AstraZeneca, Lilly Diabetes, Sanofi. L.Laviola: Advisory Panel; Lilly Diabetes, Novo Nordisk, Roche Diabetes Care, Sanofi, Speaker's Bureau; A. Menarini Diagnostics, Abbott Diabetes, Medtronic, Terumo Corporation. A.Pezzolla: None.

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