Anti-obesity Effects of Polymethoxyflavone-Rich Fraction from Jinkyool (Citrus sunki Hort. ex Tanaka) Leaf on Obese Mice Induced by High-Fat Diet

Polymethoxyflavones (PMFs) are flavonoids exclusively found in certain citrus fruits and have been reported to be beneficial to human health. Most studies have been conducted with PMFs isolated from citrus peels, while there is no study on PMFs isolated from leaves. In this study, we prepared PMF-rich fraction (PRF) from leaf of Citrus sunki Hort ex. Tanaka (Jinkyool) and investigated whether PRF can improve metabolic decline in obese mice induced by high-fat diet (HFD) for five weeks. HFD induced obese mice were assigned into HFD, OR (HFD + orlistat 15.6 mg/kg of body weight/day), and PRF (HFD + 50, 100, 200 mg/kg of body weight/day) groups. Orlistat and PRE were orally administrated for 5 weeks. At the end of experiment, serum biochemical parameters, histology and protein expression profiles were investigated in the tissues of each group. The body weight gain of obese mice was significantly reduced after orlistat and PRF administration for five weeks. PRE effectively improved HFD-induced insulin resistance and dyslipidemia. Histological analysis in liver demonstrated that PRF potentially improved the liver function as it inhibited the incidence of fatty liver. Moreover, PRF increased the phosphorylation of activated AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and hormone-sensitive lipase (HSL) in HFD-induced obese mice. Moreover, the liver transcriptome analysis revealed that PRE administration enriched the genes, which were mainly fatty acid metabolism. Overall, these results indicated that PRF exert anti-obesity effect by modulation of lipid metabolism. Liver RNA profiles of C57BL/6J mice were generated by mRNA sequencing, using Illumina NovaSeq 6000.