Comparison Treatments of Oleanolic acid and Metformin on Lipid Metabolism of Rats (Rattus norvegicus) with Metabolic Dysfunction

Abstract

The World Health Organization indicated that the world 's population living with obesity has doubled to 13% since the 1980s, affecting more than 600 million adults and 42 million children under the age of 5 years in 2014. This indicates that obesity has become a global epidemic that is growing at an alarming rate. As a risk factor to metabolic dysfunctions, obesity results in high mortalities both in children and adults, and continues to reduce life expectancies of individuals across the globe. The aim of this study is to identify, compare and describe the effects of Oleanolic acid and Metformin on lipids (free fatty acids) and genes/protein metabolism in vivo, using a neonatal rodent model. The study was performed on litters of 40 dams (Rattus norvegicus) each with an average of 8-12 pups. The pups were randomly assigned to either Control (C) [20% of DMSO water], oleanolic acid (60 mg/kg), metformin (500 mg/kg), high fructose diet (25% w/v of Fructose (HFD), a combination of oleanolic acid (OA) and high fructose diet solution (OA/HFD), and metformin and high fructose diet solution (Met/HFD). Lipid extraction and purification were performed and identification of free fatty acids was done using gas chromatography- mass spectrometry. RNA extraction, cDNA synthesis and qPCR on skeletal muscle samples was used to analyse the following genes; GLUT-4, FAS, ACC-1 , NRF-1, Aldolase B, GLUT-5, PPARy and CPT-1 . The HFD treated rats had high levels of saturated FFAs; dodecanoic and stearic acids, which were associated with increased lactic acid, decreased glucose, supressed expression of GLUT-4, NRF-1 and CPT-1 genes, and increased expression of ACC-1 (P<0.01) and FAS. OA/HFD and MET/HFD groups were found to have increased levels of both mono- and polyunsaturated FFAs; glycolic, oleic, docosahexaenoic and octadecadienoic acids better than those of HFD group. These unsaturated FFAs were associated with increased expression of GLUT-4 (P<0.01) and NRF-1 (P<0.01) and decreased expressions of both ACC-1 and FAS (P<0.05). Our findings show that neonatal oral administration of both OA and MET improve fatty acid oxidation and carbohydrates metabolism in skeletal muscles in vivo. Our findings also showed that fructose accelerates accumulation of saturated FFAs within skeletal muscles.