410-P: Effects of Palmitate and Oleate on Apoptosis, Autophagy, Stress, Kinase Phosphorylation, and Enzymes of Fatty Acid Oxidation in Human Cardiac Progenitor Cells from Control and Diabetic Subjects

• Published in: Diabetes (New York, N.Y.) Vol. 69; no. Supplement_1
• Main Authors: LAVIOLA, LUIGI, SCHIPANI, ROSSELLA, DORIA, ROSSELLA, CACCIOPPOLI, CRISTINA, LEONARDINI, ANNA, NATALICCHIO, ANNALISA, PERRINI, SEBASTIO, CIGNARELLI, ANGELO, GIORGINO, FRANCESCO
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.06.2020
• Subjects: Apoptosis; Autophagy; c-Jun protein; Cardiovascular diseases; Carnitine palmitoyltransferase; Caspase-3; Cytotoxicity; Diabetes; Diabetes mellitus; Enzyme-linked immunosorbent assay; Enzymes; Fatty acids; Heart; Immunoblotting; MAP kinase; Mitochondria; mRNA; Oxidation; Palmitic acid; Palmitoyltransferase; Phagocytosis; Phosphorylation; Progenitor cells; Stem cells; Supplements; Transcription factors
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db20-410-P

Elevated circulating levels of palmitate are associated with high cardiovascular risk in diabetes. In contrast, oleate prevents palmitate-induced cytotoxic stress in multiple cell types. The viability of cardiac progenitor cells (CPC) is essential for tissue renewal in the heart. In this study, the ability of palmitate and oleate to induce apoptosis, autophagy and stress kinase phosphorylation, as well as the effects on enzymes involved in fatty acid oxidation, were investigated in human CPC isolated from control subjects or type 2 diabetic patients. Palmitate, but not oleate, induced apoptosis in control and diabetic CPC, as assessed by caspase-3 cleavage and ELISA assay (p<0.05). Exposure of control and diabetic CPC to 0.25 mM palmitate for 16 h also resulted in increased autophagy, evidenced by light chain 3-II immunoblotting (p<0.05). In contrast, oleate did not induce autophagy. Palmitate, but not oleate, also induced p38 MAPK and c-Jun phosphorylation (p<0.05), in control and diabetic CPC. Importantly, the palmitate effects on apoptosis and autophagy, as well as stress kinase activation, were prevented in control and diabetic CPC co-treated with 0.1 mM oleate for 16 h (p<0.05). However, palmitate, alone or with oleate, increased the mRNA levels of carnitine palmitoyltransferase 1B (CPT1B) (p<0.05), one of the enzymes of mitochondrial fatty acid oxidation, in control CPC but not in diabetic CPC. In conclusion, oleate prevents palmitate-induced apoptosis, autophagy and p38 MAPK and JNK signaling in CPC from control subjects and diabetic patients. Since palmitate increases CPT1B expression only in control CPC, a selective impairment in metabolic signaling appears to occur in diabetic CPC. Hence, oleate supplementation might preserve the viability of cardiac progenitors from the lipotoxic damage in both control and diabetic subjects.