Onion peel extract increases hepatic low-density lipoprotein receptor and ATP-binding cassette transporter A1 messenger RNA expressions in Sprague-Dawley rats fed a high-fat diet

Abstract

In the present study, we hypothesized that onion peel extract (OPE) alters hepatic gene expression to improve blood cholesterol profiles. To investigate the effect of OPE to test our hypothesis, Sprague-Dawley rats were fed ad libitum for 8 weeks with the control, high-fat diet (HFD) or the high-fat diet with 0.2% OPE supplementations (HFD + OPE). Messenger RNA (mRNA) levels of genes in cholesterol metabolism and fatty acid metabolism were examined by semiquantitative reverse transcriptase polymerase chain reaction. The OPE in HFD reverted high fat–induced reduction in mRNA levels of sterol regulatory element-binding protein-2, low-density lipoprotein receptor, and hydroxyl-3-methylglutaryl coenzyme reductase genes in the liver comparable with the levels of the control group. Onion peel extract slightly increased stearoyl-coA desaturase 1 (SCD-1) expression compared with high-fat feeding. However, sterol regulatory element-binding protein-1c and fatty acid synthase were not affected by high-fat or OPE feeding. Onion peel extract also enhanced expression of ATP-binding cassette transporter A1, peroxisome proliferator–activated receptor γ2 and scavenger receptor class B type I genes when compared with high-fat feeding. However, OPE did not influence high fat–triggered changes in apolipoprotein A1 mRNA levels and liver X receptor α were not affected by either high-fat or OPE feeding. Our results suggest that OPE changes the expression of genes associated with cholesterol metabolism in favor of lowering blood low-density lipoprotein cholesterol and enhancing high-density lipoprotein cholesterol through increasing mRNA abundance of low-density lipoprotein receptor and ATP-binding cassette transporter A1 genes.

Introduction

Abnormal blood lipid profiles have been highly associated with an increased risk for metabolic disorders such as cardiovascular diseases (CVDs) [1]. It is well demonstrated that an elevated blood cholesterol level is known for a primary condition contributing to CVD [2], [3]. Also, recent clinical trials using statins showed that a decrease in blood low-density lipoprotein (LDL) cholesterol reduces cardiovascular risk [4]. In addition, epidemiologic evidence has reported that low levels of serum high-density lipoprotein (HDL) cholesterol were associated with increased CVD morbidity and mortality [3]. In this regard, the strategy for ameliorating blood lipid profiles has been suggested to confer cardiovascular protective effects.

Numerous data from epidemiologic and clinical studies have indicated a relationship between dietary intake of flavonoids and reduced risk of CVD [5], [6]. Onion is among the most highly consumed vegetables worldwide, which contains many different forms of flavonoids, predominantly quercetin, and smaller quantities of kaempferol, isorhamnetin, anthocyanin, and taxifolin [7]. Besides quercetin, there are quercetin derivatives where glycosyl moieties are found in different positions of the molecule [8], [9]. Many epidemiologic and animal studies suggest beneficial health effects of flavonoids and organosulfur compounds, which are abundant in onions [10], including antidiabetic, anticancer, and antifungal activity [11], [12], [13], [14].

We previously reported the beneficial effects of onion supplementation in improving lipid metabolism in humans [15], [16], suggesting it as an alternative and/or supplementary option for the prevention of CVD. For example, 12-week onion powder displayed significant reductions in circulating levels of total cholesterol and LDL cholesterol in hyperlipidemic patients [15]. Also, it was demonstrated that 10-week supplementation of quercetin-rich onion extract lowered serum levels of LDL cholesterol and increased serum levels of HDL cholesterol in male smokers [16]. Although accumulating data have reported positive effects of onion supplementation on lipid metabolism, the exact underlying mechanism explaining these effects is still unclear. In the current study, we hypothesized that onion peel extract (OPE) changes the expression of hepatic genes for cholesterol metabolism to modulate blood cholesterol levels. Therefore, we investigated whether the effects of OPE supplementation could modulate hepatic messenger RNA (mRNA) expression of genes regulating cholesterol homeostasis in rats with diet-induced hypercholesterolemia, which were extended from a previous study [17]. Our results may provide a mechanism to support the idea that the quercetin-rich OPE could modulate hepatic gene expression to ameliorate dysregulated blood lipid profiles.