Potential Protective Effects of Neonatal Supplementation with Oleanolic Acid on Peroxisome Proliferator-Activated Receptor Gamma (PPARγ)-Ligand Dependent Regulation of Glucose Homeostasis in High Fructose-Fed Rats

Abstract

The effect of neonatal oral supplementation of oleanolic acid (OA) on peroxisome proliferator-activated receptor gamma (PPARγ)-1 on glucose homeostasis in high fructose-fed rats was investigated. Rat pups (7 days old) were randomly assigned to and randomly administered with control (Distilled water, DW), OA (60 mg/kg), metformin (MET, 500 mg/kg), high fructose solution (HFS, 20% w/v), OA + HFS, MET + HFS, and treated till postnatal day (PND) 14. The pups were weaned onto a standard diet on PND 21 up to PND 111 and terminated on PND 112. Glucose derivatives and gene expressions of PPARγ-1 and glucose transporter type 4 (Glut-4) in the skeletal muscles were determined by using reverse transcription-quantitative polymerase chain reaction and gas chromatography-mass spectrometry, respectively. HFS significantly lowered glucose concentration and showed the propensity to suppress the expression of PPARγ-1, but not significantly. OA and MET alone significantly increased PPARγ-1 and Glut-4 expressions. There was no significant difference between the OA and OA + HFS for PPARγ-1 and Glut-4 expressions, although OA expressions were always higher than that of the OA + HFS group. An elevated level of glucose-6-phosphate was observed in OA, MET, and OA + HFS groups. Ribose-5-phosphate was significantly higher in OA and MET groups than the control. Ribose-5-phosphate was also significantly high in OA-treated group compared with OA + HFS. It is concluded that the neonatal supplementation with OA could help to improve the activity of PPARγ in reducing the burden of metabolic diseases.