Effects of peroxisome proliferator activated receptor gamma (PPARɣ) agonist on fasting model applied neuron cultures

Abstract

Abstract Objectives Peroxisome proliferator activated receptor gamma (PPARγ) agonists used for the treatment of Diabetes Mellitus (DM), has important roles on the regulation of metabolism including ketogenesis in fasting and low glucose states. Recently PPARγ was proven to have anti-oxidant and anti-inflammatory effects on neuronal cells. Methods In the present study, effects of pioglitazone (PPARγ agonist) on cell survival, energy metabolism and mitochondrial functions were investigated in glucose deprived fasting model applied SH-SY5Y (ATCC/CRL 2266) cell lines. Before and after pioglitazone treatment; energy metabolites (glucose, lactate, ketone (βOHB), lactate dehydrogenase activity), mitochondrial citrate synthase activity and cell viability were investigated. Results and Conclusions PPARγ agonist addition to glucose deprived, ketone added neurons provided positive improvements in energy metabolites (p<0.01), mitochondrial functions (p<0.001) and survival rates (p<0.01). Changes in mitochondrial citrate synthase activity, lactate and LDH levels of neuronal cells treated with PPARγ agonist have not been previously shown. Our results suggest, pioglitazone as an effective alternative for the treatment of neurodegenerative diseases especially with the presence of ketone bodies. By clarifying the mechanisms of PPARγ agonists, a great contribution will be made to the treatment of neurodegenerative diseases.