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.
Highlights
In recent years, effects of calorie restriction (CR) and prolonged fasting on brain functions have been studied in experimental and clinical studies
Final concentration of 5 μM pioglitazone was added to the neurons that were incubated with normal (N) and fasting (F) medium in order to see the effects of piaglitazone on metabolic parameters and viability of the cells and no statistically significant effect was detected on the cells
Effects of peroxisome proliferator activated receptor gamma (PPARγ) agonist on glucose deprived, ketone added neuron cultures in terms of neuron viability, energy metabolism and mitochondrial functions were investigated in order to evaluate alternative treatment options in neurodegenerative diseases
Summary
Effects of calorie restriction (CR) and prolonged fasting on brain functions have been studied in experimental and clinical studies. In both cases, since there is a glucose restriction, brain uses ketone bodies as an alternative energy source. Our group is working on the effects of the prolonged fasting model, an alternative to ketogenic diet, and ketone bodies in humans and neuronal cells. The present study is inspired by the newly discovered positive effects of peroxisome proliferator-activated receptor (PPAR) gamma agonists (PPARγ), used for the treatment of Diabetes Mellitus (DM), on neuron and mitochondrial damage [2, 3]. In prolonged fasting ketone bodies, secreted in high concentrations, can activate PPARγ pathways
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