441-P: Oleate Prevents Palmitate-Induced Abnormalities in Insulin Signaling in Human Cardiac Progenitor Cells by Inhibiting p38 MAPK and c-Jun Phosphorylation

• Published in: Diabetes (New York, N.Y.) Vol. 71; no. Supplement_1
• Main Authors: DORIA, ROSSELLA, CALDERONI, ISABELLA, CACCIOPPOLI, CRISTINA, GENCHI, VALENTINA ANNAMARIA, SANTARPINO, GIUSEPPE, LEONARDINI, ANNA, NATALICCHIO, ANNALISA, PERRINI, SEBASTIO, CIGNARELLI, ANGELO, GIORGINO, FRANCESCO, LAVIOLA, LUIGI
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01-06-2022
• Subjects: Acid deposition; AKT protein; Auricle; Biopsy; c-Jun protein; Cardiovascular diseases; Diabetes; Fatty acids; Gene expression; Heart; Homeostasis; Insulin; Insulin resistance; Isoforms; Kinases; MAP kinase; mRNA; Myocardium; Palmitic acid; Phosphorylation; Progenitor cells; Stem cells; Supplements; Transcription factors
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db22-441-P

Elevated saturated fatty acid deposition in the heart results in insulin resistance, stress kinase activation, and increased cardiovascular risk in humans. The viability of human cardiac progenitor cells (hCPC) is essential for myocardium homeostasis. This study investigates the ability of palmitate, a saturated fatty acid, to impair insulin signaling in hCPC isolated from right auricle biopsies, and the potential protective effects of oleate, a mono-unsaturated fatty acid. hCPC were found to express both insulin receptor (IR) isoforms, IR-A and IR-B, with higher IR-A:IR-B ratio. Exposure of hCPC to 100 nM insulin for 15 min induced Akt (S473) phosphorylation (p<0.05) . However, treatment with 0.25 mM palmitate, but not with 0.1 mM oleate, for 24 h resulted in impaired insulin-induced Akt phosphorylation (p<0.05) with no effect on total Akt protein levels. Palmitate, but not oleate, also induced p38 MAPK (T180/Y182) and c-Jun (S63) phosphorylation (p<0.05) . Pretreatment for 1 h with 15 µM SB202190, a p38 MAPK inhibitor, or with 20 µM SP600125, a JNK inhibitor, significantly inhibited the ability of palmitate to impair insulin-induced Akt phosphorylation (p<0.05) . Interestingly, co-incubation of palmitate with oleate abolished the palmitate-induced p38 MAPK and c-Jun phosphorylation (p<0.05) and inhibition of insulin-induced Akt phosphorylation (p<0.05) . In addition, palmitate, but not oleate, was associated with downregulation of IR protein levels (p<0.05) , although with increased expression of total IR mRNA, IR-A, IR-B, and increased IR-A/IR-B ratio (p<0.05) . Co-incubation with oleate also prevented the palmitate-induced changes in IR (p<0.05) .
In conclusion, oleate prevents the palmitate-induced abnormalities in insulin signaling in hCPC, largely by counteracting p38 MAPK and JNK activation. Hence, oleate supplementation might limit lipotoxicity, thus contributing to cardiac protection.