Proteomic analysis of hepatic proteins in high fat diet mice in response to the feeding of Toona Sinensis ethanol extract

Abstract

The major pathogenesis of metabolic syndrome is the development of insulin resistance, which promotes the elevation of blood pressure, dyslipidemia, and dysregulation of glucose metabolism. Among the target tissues of insulin, liver is the principal regulator of glucose and lipid metabolism by controlling hepatic glucose production, glycogen storage and lipogenesis. Toona sinnesis (TS) has been reported to be beneficial for metabolic syndrome, however the effect of TS on liver metabolism is not clear. In the present study, proteomics analysis and Western blot were used to investigate the effect of TSL-E on the high-fat diet (HFD) fed mice. The anti-oxidation activity and lipid lowering effect were investigated by measurement of mitochondria membrane potential (MMP) and Oil-red-O staining. Using the 2D-gel proteomic analysis followed by mass spectrometry identification, we found a clear distinction in differential expression of oxidative stress, glucose metabolism and lipid metabolism related proteins responding TSL-E. HFD up regulated sorbitol dehydrogenase (SDH), UDP-6 glucose dehydrogenase (UDGH), glutamate dehydrogenase (GDH) proteins expression suggested that HFD increased gluconeogenesis in liver of mice. In the other hand, HFD+TSL-E inhibited the increasing of gluconeogenesis in HFD by restored SDH, UDGH, GDH protein expression that were confirmed by decreased of phosphoenolpyruvate carboxykinase 2 (PCK2). While HFD increased heat shock protein 70 kda (HSP70), Catalase (Cat), HSPd1 and decreased peroxiredoxin 6 (Prdx6) proteins expression, HFD+TSL-E increased Prdx6 and restored HSP70, Hspd1 and Cat proteins expression, indicated that TSL-E exhibited anti-oxidant activity. TSL-E also shown high peroxisome proliferator-activated receptor alpha/gamma (PPARalpha/gamma)-dependent luciferase activity that confirmed by increased the expression of PPARalpha/gamma in liver of HFD mice treated with TSL-E. In conclusion, TSL-E improved the dyslipidemia of high fat diet mice through activation of PPARalpha/gamma, reduction of oxidative stress and decreasing gluconeogenesis by inhibition of the activation of the polyol pathway