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Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it matches daily obligatory losses. Several dietary factors can modify iron absorption. Polyphenols are plentiful in human diet and many compounds, including quercetin – the most abundant dietary polyphenol – are potent iron chelators. The aim of this study was to investigate the acute and longer-term effects of quercetin on intestinal iron metabolism. Acute exposure of rat duodenal mucosa to quercetin increased apical iron uptake but decreased subsequent basolateral iron efflux into the circulation. Quercetin binds iron between its 3-hydroxyl and 4-carbonyl groups and methylation of the 3-hydroxyl group negated both the increase in apical uptake and the inhibition of basolateral iron release, suggesting that the acute effects of quercetin on iron transport were due to iron chelation. In longer-term studies, rats were administered quercetin by a single gavage and iron transporter expression measured 18 h later. Duodenal FPN expression was decreased in quercetin-treated rats. This effect was recapitulated in Caco-2 cells exposed to quercetin for 18 h. Reporter assays in Caco-2 cells indicated that repression of FPN by quercetin was not a transcriptional event but might be mediated by miRNA interaction with the FPN 3′UTR. Our study highlights a novel mechanism for the regulation of iron bioavailability by dietary polyphenols. Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption.

Ghrelin is a 28-residue peptide hormone that is principally released from the stomach during fasting and prior to eating. Two forms are present in human plasma: the unmodified peptide and a less abundant acylated version, in which octanoic acid is attached to the third residue, a serine, via an ester linkage. The acylated form of ghrelin acts as a ligand for the growth hormone secretagogue receptor and can stimulate the release of growth hormone from the pituitary gland. It also initiates behavioral and metabolic adaptations to fasting. Here we show that an immobilized form of ghrelin specifically binds a species of high density lipoprotein associated with the plasma esterase, paraoxonase, and clusterin. Both free ghrelin and paraoxon, a substrate for paraoxonase, can inhibit this interaction. An endogenous species of ghrelin is found to co-purify with high density lipoprotein during density gradient centrifugation and subsequent gel filtration. This interaction links the orexigenic peptide hormone ghrelin to lipid transport and metabolism. Furthermore, the interaction of the esterified hormone ghrelin with a species of HDL containing an esterase suggests a possible mechanism for the conversion of ghrelin to des-acyl ghrelin.Ghrelin is a peptide hormone that was purified from the stomach that can cause the release of growth hormone from the anterior pituitary gland (1). It has subsequently been found that ghrelin is predominantly released from the stomach prior to feeding (2), although other tissues have been shown to express the gene as well (3). Peripheral injections of ghrelin have been shown to increase feeding in both rats (4) and humans (5), and a course of injections leads to increased obesity in rats (4). Therefore, ghrelin can be seen as an important link between the stomach, appetite, and metabolism as well as playing a role in growth hormone release.The aim of this study was to establish whether ghrelin interacts with any other component of plasma. It was hypothesized that any interaction might be an important factor in determining the activity or longevity of ghrelin in plasma. Furthermore, an interaction in the plasma might be involved in the creation of the two distinct forms of ghrelin (6): the acylated form, in which octanoic acid is covalently bound to the peptide, and the more prevalent des-acyl form in which the peptide is unmodified. The acylated form of ghrelin stimulates the release of growth hormone from the pituitary gland, therefore any mechanism that might convert one form of ghrelin into the other could be an important factor in controlling the activity of ghrelin. MATERIALS AND METHODSA peptide corresponding to mature human ghrelin, with a cysteine residue substituted for the serine residue at the third position (S3C ghrelin), was synthesized by Fmoc 1 chemistry using a Rainin PS3 automatic peptide synthesizer (Protein Technologies). The peptide was purified to over 90% homogeneity by reverse-phase chromatography using a Varian 500LC HPLC. The molecular weight of the purified peptide ...