Citrus junos Tanaka peel ameliorates hepatic lipid accumulation in HepG2 cells and in mice fed a high-cholesterol diet.

Eun Ju Shin,Jae Ho Park,Jin-Taek Hwang,Mi Jeong Sung,Min-Yu Chung

doi:10.1186/s12906-016-1460-y

Abstract

Background Citrus junos Tanaka (yuja), a yellow-coloured citrus fruit has traditionally been consumed in Korea, Japan, and China and has been found effective in preventing certain diseases. However, the inhibitory effect of yuja on hepatic lipid accumulation has not been clearly elucidated thus far.MethodsThe inhibitory effect of yuja on hepatic lipid accumulation was investigated in both cell culture and mouse models. We investigated the inhibitory effect of ethanol extract of yuja peel (YE) using HepG2 cells. We next confirmed the effect of YE in mice fed a high cholesterol diet. Animals were divided into 4 groups (n = 8): a normal diet group (ND), a high-cholesterol diet group (HC), high-cholesterol diet plus 1% YE (YL), high-cholesterol diet plus 5% YE (YH).ResultSeventy percent ethanolic extracts of yuja peel (YE) reduced oleic acid-induced hepatic lipid accumulation in HepG2 cells. Treatment with YE at 100, 200 μg/mL up-regulated expression levels of cholesterol metabolism-related proteins such as AMPK, ACC, PPAR-α, and CPT1 and down-regulated the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase. The hypocholesterolemic effect of YE was further confirmed in mice fed a high-cholesterol diet. Compared to ND (normal diet) mice, HC (high-cholesterol diet) mice showed increased body weight, liver fat content, liver weight, and content of total cholesterol and low-density lipoprotein (LDL) cholesterol. On the contrary, administrations of YL (HC + 1% YE) or YH (HC + 5% YE) significantly reduced body weight, liver fat content, liver weight, total cholesterol, and LDL cholesterol compared to those of only HC fed mice group. As a result of in vitro data, protein expressions of PPAR-α and CPT1 were induced in mice fed YE diet compared to HC diet but HMGCR expression was decreased.ConclusionsYuja peel ameliorates hepatic lipid accumulation in both cell culture and mouse models and therefore, could serve as a useful supplement for hypercholesterolemia.

Highlights

Citrus junos Tanaka, a yellow-coloured citrus fruit has traditionally been consumed in Korea, Japan, and China and has been found effective in preventing certain diseases
Hydroxy-3Methylglutaryl-Coenzyme A Reductase (HMGCR) is inhibited by statins, which upregulate the expression of low-density lipoprotein (LDL) receptors in the liver, resulting in increased catabolism of plasma LDL and decreased plasma cholesterol [5]
Co-treatment with oleic acid (OA) and yuja peel (YE) induced Peroxisome Proliferator-Activated Receptor-α (PPAR-α) and CPT1 expression (Fig. 2b). These results indicated that YE inhibited OA-induced hepatic lipid accumulation via AMPK signalling, in particular, by stimulating PPAR-α and CPT1, β-oxidation-related proteins and reducing HMGCR proteins involved in lipogenesis

Summary

Introduction

Citrus junos Tanaka (yuja), a yellow-coloured citrus fruit has traditionally been consumed in Korea, Japan, and China and has been found effective in preventing certain diseases. The inhibitory effect of yuja on hepatic lipid accumulation has not been clearly elucidated far. Lifestyle-related diseases including hepatic lipid accumulation are associated with irregular lifestyle and diet. Reduction of total cholesterol and LDL cholesterol levels may be a significant strategy for preventing atherosclerosis. Another mechanism of preventing hypercholesterolemia includes targeting enzymes including AMPK and 3hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). AMPK is a metabolic protein, which plays a central role in lipid metabolism and inhibits anabolic pathways, including cholesterol synthesis by targeting HMGCR [4]. HMGCR is a rate-limiting enzyme in cholesterol synthesis pathway; it is suppressed by cholesterol derived from the degradation of LDL via the LDL receptor [5]. AMPK and HMGCR enzymes are the targets of various cholesterollowering natural ingredients

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