Oleuropein-Rich Jasminum Grandiflorum Flower Extract Regulates the LKB1-PGC-1 Axis Related to the Attenuation of Hepatocellular Lipid Dysmetabolism

Diets rich in fat are a major cause of metabolic disease, and nutritional food has been widely used to counteract the metabolic disorders such as obesity and fatty liver. The present study investigated the effects of oleuropein-enriched extract from Jasminum grandiflorum L. flowers (OLE-JGF) in high-fat diet (HFD)-fed mice and oleic acid (OA)-treated AML-12 cells. Treatment of HFD-fed mice with 0.6% OLE-JGF for 8 weeks significantly reduced body and liver weights, as well as attenuating lipid dysmetabolism and hepatic steatosis. OLE-JGF administration prominently suppressed the mRNA expressions of monocyte chemoattractant protein-1 (MCP-1) and cluster of differentiation 68 (CD68), and it also downregulated acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) as well as sterol-regulatory-element-binding protein (SREBP-1c) in the liver. Meanwhile, mitochondrial DNA and uncoupling protein 2 (UCP2) were upregulated along with the increased expression of mitochondrial biogenic promoters including liver kinase B1 (LKB1), peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), nuclear factor-erythroid-derived 2-like 2 (Nrf2), and mitochondrial transcription factor A (Tfam), but did not change AMP-activated protein kinase (AMPK) in liver. The lipid droplets were decreased significantly after treatment with 80 mu M oleuropein for 24 h in OA-induced AML-12 cells. Furthermore, oleuropein significantly inhibited ACC mRNA expression and upregulated LKB1, PGC-1 alpha, and Tfam mRNA levels, as well as increasing the binding level of LKB1 to PGC-1 alpha promoter in OA-induced cells. These findings indicate that OLE-JGF reduces hepatic lipid deposition in HFD-fed mice, as well as the fact that OA-induced liver cells may be partly attributed to upregulation of the LKB1-PGC-1 alpha axis, which mediates hepatic lipogenesis and mitochondrial biogenesis. Our study provides a scientific basis for the benefits and potential use of the J. grandiflorum flower as a food supplement for the prevention and treatment of metabolic disease.