EN
Abstract:
Introduction: Diabetes is a major contributor to
cardiovascular disease. There is a growing body of evidence
pointing towards intra-myocellular lipid accumulation as
an integral etiological factor. Here we aimed to determine
the effect of two common fatty acids on lipid accumulation
and cellular stress in primary cardiomyocytes. Methods: We evaluated lipid accumulation biochemically
(by triacylglyceride assay and radiolabeled fatty acid
uptake assay) as well as histologically (by BODIPY 493/503
staining) in mouse and rat neonatal cardiomyocytes
treated with saturated (palmitate) or mono-unsaturated
(oleate) fatty acids. Endoplasmic reticulum (ER) stress was
evaluated by quantitative reverse transcription polymerase
chain reaction (qRT-PCR) and Western blotting. Cell
viability was assessed by propidium iodide staining. Results: We found that both oleate and palmitate
led to significant increases in intracellular lipid in
cardiomyocytes; however there were distinct differences
in the qualitative nature of BODIPY staining between
oleate and palmitate treated cardiomyocytes. We also
show that palmitate caused significant apoptotic cell
death and this was associated with ER stress. Interestingly,
co-administration of oleate with palmitate abolished cell
death, and ER stress. Finally, palmitate treatment caused
a significant increase in ubiquitination of Grp78, a key
compensatory ER chaperone. Conclusion: Palmitate causes ER stress and apoptotic cell
death in primary cardiomyocytes and this is associated
with apparent differences in BODIPY staining compared
to oleate treated cardiomyocytes. Importantly, the
lipotoxic effects of palmitate are abolished with the
co-administration of oleate.