It is known that exposure to excess
saturated fatty acids, especially
palmitate, can trigger cellular stress responses interpreted as lipotoxicity. The effect of excessive
free fatty acids on oxidative phosphorylation capacity in myoblasts of patients with the m.3243A>G mutation was evaluated with the mitochondrial (Mito) stress test using a Seahorse XF96 analyzer. ß-oxidation, measured with the Seahorse XF96 analyzer, was similar in patients and controls, and reduced in both patients and controls at 40 °C compared to 37 °C. Mito stress test in the absence of
fatty acids showed lower values in patients compared to controls. The mitochondrial activity and
ATP production rates were significantly reduced in presence of
palmitate, but not of
oleate in patients, showing a negative effect of excessive
palmitate on mitochondrial function in patients.
Diabetes mellitus is a frequent symptom in patients with m.3243A>G mutation. It can be speculated that the negative effect of
palmitate on mitochondrial function might be related to
diacylglycerols (DAG) and
ceramides (CER) mediated
insulin resistance. This might contribute to the elevated risk for
diabetes mellitus in m.3243A>G patients.