Eugeniin improves cholesterol metabolism in HepG2 cells and Caco-2 cells.

Considering the absence of prior studies on the cholesterol metabolism-improving effects of eugeniin, the present investigation aimed to explore the potential impact of eugeniin on cholesterol metabolism. This study sought to elucidate the molecular mechanisms involved in this process using HepG2 and Caco-2 cells treated with 5 µm eugeniin. The intracellular cholesterol levels in HepG2 and Caco-2 cells were significantly decreased in the 24-h eugeniin-treated group. The protein and messenger ribonucleic acid (mRNA) levels of the low-density lipoprotein receptor (LDLR) were increased, while 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase protein and mRNA levels were decreased in HepG2 cells 6 h of the eugeniin-treated group. Additionally, LDLR protein and mRNA levels were increased in HepG2 cells after 24 h of eugeniin treatment. In Caco-2, the protein and mRNA levels of ATP-binding cassette transporter 1 were increased after 24 h eugeniin treatment. This novel finding indicates that eugeniin improves cholesterol metabolism in human cell cultures.

Rose polyphenols exert antiobesity effect in high-fat-induced obese mice by regulating lipogenic gene expression.

Obesity presents a major risk factor in the development of cardiovascular diseases. Recent reports indicate that many kinds of polyphenols have the potential to prevent metabolic diseases. We hypothesized that rose polyphenols (ROSE) have the effect of improvement in lipid metabolism. In this study, we investigated whether rose polyphenols affected lipid metabolism and exerted antiobesity. To clarify the mechanism, C57BL/6J mice were fed a high-fat diet containing 0.25% ROSE for 35 days. Compared with the control group, body weight gain and adipose tissue weight in the 0.25% ROSE group were significantly decreased. Serum cholesterol and hepatic triglyceride concentrations significantly decreased, whereas fecal triglyceride was significantly increased in the 0.25% ROSE group. Liver stearoyl-CoA desaturase 1 (Scd1), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), and acyl-CoA:cholesterol acyltransferase 1 (Acat1) mRNA as well as protein stearoyl-CoA desaturase 1 concentrations were significantly lower in the 0.25% ROSE group than that in the control group. The mRNA and the protein concentrations of adipose triglyceride lipase, hormone-sensitive lipase, and peroxisomal acylcoenzyme A oxidase 1 in white adipose tissue were significantly higher in the 0.25% ROSE group than that in the control group. The components in rose polyphenols were quantified by liquid chromatography-tandem mass spectrometry, and we consider that ellagic acid plays an important role in an antiobesity effect because the ellagic acid content is the highest among polyphenols in rose polyphenols. In summary, rose polyphenols exhibit antiobesity effects by influencing lipid metabolism-related genes and proteins to promote lipolysis and suppress lipid synthesis.

Comparison of the slow-pull and aspiration methods of endobronchial ultrasound-guided transbronchial needle aspiration for next-generation sequencing-compatible tissue collection in non-small cell lung cancer.

BACKGROUND: Personalized treatment for non-small cell lung cancer (NSCLC) has advanced rapidly, and elucidating the genetic changes that trigger this disease is crucial for appropriate treatment selection. Both slow-pull and aspiration methods of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are accepted methods for collecting samples suitable for next-generation sequencing (NGS) to examine driver gene mutations and translocations in NSCLC. Here, we aimed to determine which of these two methods is superior for obtaining higher-quality samples from patients with NSCLC. METHODS: Seventy-one patients diagnosed with NSCLC via EBUS-TBNA using the slow-pull or aspiration (20-mL negative pressure) methods between July 2019 and September 2022 were included. A total of 203 tissue samples from the 71 patients were fixed in formalin, embedded in paraffin, and mounted on slides. The presence of tissue cores, degree of blood contamination, and number of tumor cells were compared between the groups. The success rate of NGS, using Oncomine Dx Target Test Multi-CDx, was also compared between the groups. RESULTS: The slow-pull method was associated with a higher yield of tissue cores, lower degree of blood contamination, and higher number of tumor cells than the aspiration method. The success rate of the NGS was also significantly higher for the slow-pull group (95%) than for the aspiration group (68%). CONCLUSION: Overall, these findings suggest that the slow-pull method is a superior technique for EBUS-TBNA to obtain high-quality tissue samples for NGS. The slow-pull method may contribute to the identification of driver gene mutations and translocations and facilitate personalized treatment of NSCLC.

Pentapeptide IIAEK ameliorates cholesterol metabolism via the suppression of intestinal cholesterol absorption in mice.

Dietary protein-derived peptides are effective in improving dyslipidemia and hypercholesterolemia. We previously identified a novel cholesterol-lowering pentapeptide IIAEK from milk beta-lactoglobulin. However, it remains unclear whether IIAEK affects the micellar solubility of cholesterol and the bile acid-binding ability to lower cholesterol. Moreover, there is no direct evidence that IIAEK inhibits intestinal cholesterol absorption and affects hepatic cholesterol and fecal steroid excretion in vivo. Herein, we showed that IIAEK did not affect the micellar solubility of cholesterol and the bile acid-binding ability. However, we found that IIAEK decreased serum and liver cholesterol levels and increased fecal steroid excretion in mice. Interestingly, IIAEK markedly suppressed the intestinal absorption of [3H]-cholesterol in mice. In conclusion, we found that IIAEK ameliorated cholesterol metabolism by suppressing intestinal cholesterol absorption without affecting in vitro micellar solubility of cholesterol and the bile acid-binding ability in mice.

Predictors of lung injury during durvalumab maintenance therapy following concurrent chemoradiotherapy in unresectable locally advanced non-small cell lung carcinoma.

BACKGROUND: Based on the results of the PACIFIC trial, maintenance with durvalumab has emerged as the standard treatment following concurrent chemoradiotherapy in patients with unresectable locally advanced non-small cell lung carcinoma (NSCLC). However, adverse events attributed to durvalumab, especially lung injuries, including immune-related adverse events, and radiation pneumonitis, are concerning. This study retrospectively investigated the factors related to lung injury in patients receiving the PACIFIC regimen. METHODS: Patients with unresectable locally advanced NSCLC who received durvalumab maintenance therapy following concurrent chemoradiotherapy at Yokohama City University Medical Centre between July 2018 and March 2022 were included. Clinical data, volume of normal lung receiving 20 or 5 Gy or more (V20 or V5), planning target volume (PTV), and relative lung parenchyma volume in emphysematous lung receiving 20 or 5 Gy or more (RLPV20 or 5; V20 or V5/100-percentage of low-attenuation volume) were evaluated. RESULTS: Performance status (PS), V20, V5, PTV, RLPV20, and RLPV5 were significantly higher in the lung injury group in the univariate analysis. Furthermore, RLPV20 was the most significant factor in the lung injury group in the multivariate analysis comprising PS, PTV, V20, and RLPV20. CONCLUSION: RLPV20 and RLPV5 are useful in estimating lung inflammation. RLPV20 could be considered the most reliable risk factor for maintenance therapy with durvalumab following concurrent chemoradiotherapy in patients with unresectable locally advanced NSCLC.

Thymic atypical carcinoid tumors with elevated mitotic counts in a patient with multiple endocrine neoplasia: A case report.

Thymic neuroendocrine tumors associated with multiple endocrine neoplasia are only defined as carcinoid and are not associated with large-cell neuroendocrine carcinoma (LCNEC). We report the case of a multiple endocrine neoplasia type 1 patient with atypical carcinoid tumors with elevated mitotic counts (AC-h), an intermediate condition between carcinoid and LCNEC. A 27-year-old man underwent surgery for an anterior mediastinal mass and was diagnosed with thymic LCNEC. Fifteen years later, a mass appeared at the same site, which was determined to be a postoperative recurrence based on the pathological results of a needle biopsy and the clinical course. The patient's disease remained stable for 10 months on anti-programmed death-ligand 1 antibody and platinum-containing chemotherapy. The needle biopsy specimen was submitted for next-generation sequencing, which revealed a MEN1 gene mutation, and after further examination, a diagnosis of multiple endocrine neoplasia type 1 was made. A re-examination of the surgical specimen from 15 years prior showed that it corresponded to AC-h. Although thymic AC-h is classified as thymic LCNEC according to the current definition, our data suggests that a search for multiple endocrine neoplasia is warranted in such patients.

Primary tracheal small-cell carcinoma detected 11 months after surgery for pulmonary large-cell neuroendocrine carcinoma: A case report.

Primary tracheal small-cell carcinoma is rare, and is often treated using small-cell lung cancer guidelines given that no standard treatment has been established for it. We report a patient in whom nodules appeared in the trachea and left main bronchus 11 months after surgery for pulmonary large-cell neuroendocrine carcinoma; a biopsy revealed small-cell carcinoma. Given the absence of malignant lesions elsewhere in the body, the lesions were diagnosed as primary tracheal small-cell carcinoma. Respiratory failure progressed rapidly owing to airway stenosis caused by the growing lesion, and the patient required nasal high-flow therapy. However, the lesions shrank a few days after commencing first-line chemotherapy, and his respiratory failure resolved. Accelerated hyperfractionated radiotherapy was administered in conjunction with the third course of chemotherapy, and the patient ultimately achieved a complete response. Although the lesions were initially suspected of being postoperative recurrence of pulmonary large-cell neuroendocrine carcinoma, the fact that the biopsy revealed them to be primary tracheal small-cell carcinoma indicates that intra-airway nodules that appear after lung cancer surgery may possibly be primary tracheal tumors.

Protamine-derived peptide RPR (Arg-Pro-Arg) ameliorates oleic acid-induced lipogenesis via the PepT1 pathway in HepG2 cells.

The protamine-derived peptide arginine-proline-arginine (RPR) can ameliorate lifestyle-related diseases such as obesity and hypercholesterolemia. Thus, we hypothesized that the hypolipidemic activity of RPR could attenuate events leading to non-alcoholic fatty liver disease. Addition of 2 m m oleic acid (OA) to the culture medium induced fatty liver conditions in HepG2 cells. The OA + RPR group showed significantly decreased cellular or medium triglyceride (TG) level compared with the OA group. Stearoyl-CoA desaturase-1 (SCD1) or sterol regulatory element-binding protein 1 (SREBP1) protein level was significantly lower in the OA + RPR group than in the OA group. In the R + P + R amino acid mixture-treated group, the TG level was not significantly different from that in the OA-treated group. The OA + RP- or OA + PR-treated groups showed significantly decreased cellular TG level compared with the OA group. Moreover, the effect of RPR disappeared when the peptide transporter 1 (PepT1) was knocked down with a siRNA. Collectively, our results demonstrated that RPR effectively ameliorated hepatic steatosis in HepG2 cells via the PepT1 pathway.

[A Case of Achieving CR through Chemoradiotherapy for Postoperative Oligo Lymph Node Metastasis in Gastric Cancer].

We present a case of oligo lymph node metastasis in a 70s man who had previously undergone subtotal gastrectomy for advanced gastric cancer in the prepylorus. Postoperatively, adjuvant chemotherapy was administered for a duration of 1 year. During the third postoperative year, elevated tumor markers and lymph node enlargement prompted a diagnosis of lymph node metastasis. Subsequent chemoradiotherapy resulted in a complete response(CR), which has been sustained for 2 years without any recurrence. The outcomes of this case indicate that chemoradiotherapy stands as a viable treatment option for oligo lymphatic recurrence in gastric cancer.

The physiological blood concentration of phenylalanine-proline can ameliorate cholesterol metabolism in HepG2 cells.

We have previously reported that the dipeptide Phe-Pro affects lipid metabolism in vivo and in vitro, but very little is known regarding the mechanism of action of Phe-Pro after it is absorbed by the intestines via PepT1. In this study, we administered a single oral dose of Phe-Pro to rats and quantified its concentration in the portal plasma using LC-TOF/MS analysis. Additionally, the physiological blood concentration of Phe-Pro was added to the lipid accumulation model of HepG2 cells to decrease intracellular cholesterol and increase the expression of CYP7A1 and PPARα mRNA levels. Moreover, we analyzed the binding of PPARα and Phe-Pro using AlphaFold2. We found that Phe-Pro is a ligand for PPARα. To the best of our knowledge, this is the first study that shows Phe-Pro to be present in the portal plasma. We found for the first time that Phe-Pro ameliorated cholesterol metabolism in HepG2 cells.

Retrospective analysis of independent predictors of progression-free survival in patients with EGFR mutation-positive advanced non-small cell lung cancer receiving first-line osimertinib.

BACKGROUND: Clinically measurable factors affecting the progression-free survival (PFS) of patients receiving osimertinib as first-line therapy for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC) have not yet been established. METHODS: We retrospectively reviewed the medical records of 61 patients treated with osimertinib as primary therapy for EGFR mutation-positive advanced NSCLC at Yokohama City University Medical Center between August 2018 and March 2022. Our objective was to identify the independent predictors of PFS. RESULTS: The median age of participants was 74 years. Overall, 73.8% had good (0-1) Eastern Cooperative Oncology Group performance status (PS), and 98.4% had histology of adenocarcinoma. The EGFR mutation was exon19 deletion in 52.5% and exon21 L858R in 44.3% of patients. Programmed death-ligand 1 tumor proportion score >50% was observed in 21.3% and liver metastasis in 9.9% of patients. Median PFS was 19.5 months (95% confidence interval [CI]: 10.6-31.6), and overall survival was not reached. The objective response rate was 68.9%, and disease control rate was 93.4%. Multivariate analysis showed that poor PS (2-4) negatively impacted PFS (hazard ratio, 3.79; 95% CI: 1.46-9.87; p = 0.006). Median PFS in the good PS and poor PS groups was 20.4 months (95% CI: 12.4-not evaluable) and 7.2 months (95% CI: 7.2-19.5), respectively. Interstitial lung disease of all grades and grade 3 was observed as an adverse event in 6.6 and 4.9% of patients, respectively. CONCLUSION: Poor PS was associated with poor prognosis in patients with EGFR mutation-positive advanced NSCLC treated with osimertinib as first-line therapy.

Novel Approach for Simultaneous Analysis of Peptide Metabolites from Orally Administered Glycinin in Rat Bloodstream by Coumarin-Tagged MALDI-MS.

The lack of an appropriate analytical approach characterizing metabolites from dietary proteins may prevent further studies that could clarify their health benefits. In this study, we attempted to establish a novel analytical assay of peptide metabolites from glycinin using matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS), in combination with the amine derivatization technique with coumarin (Cou). Cou (30 mmol/L) derivatization of peptides under rapid (30 min) and mild (25 °C, pH 8.5) conditions caused higher MS detection of the peptides as compared to nonderivatized peptides. In addition, an MS shift of the target by Cou derivatization (+202.0 m/z) can help to easily discriminate peptide metabolites in glycinin-administered blood, by comparing the MALDI-MS spectra of Cou-derivatized plasma with those of preadministered blood. After the oral administration of glycinin (100 mg/kg) to Sprague-Dawley rats, 15 di- to tetrapeptides were successfully characterized as glycinin-derived metabolites, demonstrating that the proposed Cou-tagged MALDI-MS is an appropriate characterization technique for peptide metabolites.

Anti-Obesity and Hypocholesterolemic Actions of Protamine-Derived Peptide RPR (Arg-Pro-Arg) and Protamine in High-Fat Diet-Induced C57BL/6J Mice.

Dietary protamine can ameliorate hyperlipidemia; however, the protamine-derived active peptide and its hypolipidemic mechanism of action are unclear. Here, we report the discovery of a novel anti-obesity and hypocholesterolemic peptide, RPR (Arg-Pro-Arg), derived from protamine in mice fed a high-fat diet for 50 days. Serum cholesterol levels were significantly lower in the protamine and RPR groups than in the control group. White adipose tissue weight was significantly decreased in the protamine and RPR groups. The fecal excretion of cholesterol and bile acid was significantly higher in the protamine and RPR groups than in the control group. We also observed a significant decrease in the expression of hepatic SCD1, SREBP1, and adipocyte FAS mRNA, and significantly increased expression of hepatic PPARα and adipocyte PPARγ1 mRNA in the protamine group. These findings demonstrate that the anti-obesity effects of protamine are linked to the upregulation of adipocyte PPARγ1 and hepatic PPARα and the downregulation of hepatic SCD1 via SREBP1 and adipocyte FAS. RPR derived from protamine has a crucial role in the anti-obesity action of protamine by evaluating the effective dose of adipose tissue weight loss.

Plant-derived peptides improving lipid and glucose metabolism.

Plant protein-derived peptides, focusing especially on soybean protein-derived peptides have considerable effects on metabolic regulation and modulation such as cholesterol lowering, triglyceride lowering, anti-obesity, inhibition of fatty acid synthase, and antidiabetic effects. The molecules targeted to study the metabolic regulatory functions of the peptides included the following: intestinal cholesterol micelle, cholesterol metabolism-related genes for cholesterol lowering, triglyceride metabolism-related genes for triglyceride lowering and anti-obesity, dipeptidyl peptidase-IV (DPP-IV), α-amylase, α-glucosidase, or glucose metabolism-related genes for lowering blood glucose levels. This review article outlines the physiological functions of plant protein-derived peptides for the improvement of lipid and glucose metabolism in vitro or in vivo.

Identification of peptides in blood following oral administration of ß-conglycinin to Wistar rats.

In this study, ß-conglycinin (100 mg/kg) was orally administered to Wistar rats in order to identify peptides that may be derived from the protein in the blood. Plasma samples taken from the tail vein up to 8 h after administration were analyzed by matrix-assisted laser desorption/ionization (MALDI) and liquid chromatography-time-of-flight (LC-TOF) mass spectrometry (MS). In total, 126 signals were detected by MALDI-MS. Among the signals, nine oligopeptides (SEL, KGPL, SILGA, DSEL, GDANI, SYFV, CLQSC, GEQPRPF, and LVINEGDA) were successfully identified as ß-conglycinin-derived peptides by LC-TOF/MS at a plasma concentration of 0.75-756 pmol/mL. The results demonstrated that ß-conglycinin could be the dietary source protein for the oligopeptides produced prior to entering the circulating bloodstream of rats.

The blockade of interleukin-33 released by hepatectomy would be a promising treatment option for cholangiocarcinoma.

Interleukin-33 (IL-33), an alarmin released during tissue injury, facilitates the development of cholangiocarcinoma (CCA) in a murine model. However, it is unclear whether IL-33 is associated with human CCA. The aim of this study was to support the following hypothesis: IL-33 is released during hepatectomy for CCA, subsequently facilitating the development of subclinical CCA and eventually leading to recurrent disease. IL-33 expression was assessed in various samples from both humans and mice including resected liver and paired plasma samples collected at hepatectomy and after surgery, and its influences on recurrent disease and patient prognosis were determined. Homogenized human liver samples with high or low IL-33 expression were added to the culture medium of human CCA cells, and the changes in proliferation and migration were evaluated. To examine the effects of inhibiting the IL-33 release induced by hepatectomy, syngraft transplantation of murine CCA cells was performed in C57BL/6J mice with or without IL-33 blockade. The amount of IL-33 released into the plasma during hepatectomy correlated with the background liver expression. High expression of IL-33 in the liver was an independent risk factor for recurrence. Homogenized liver tissue strongly expressing IL-33 increased both the proliferation and migration of tumor cells. Mice who underwent hepatectomy exhibited CCA progression in the remnant liver, whereas blockade of IL-33 during hepatectomy inhibited tumor progression. Thus, we concluded that surgery for CCA with curative intent paradoxically induced IL-33 release, which facilitated CCA recurrence, and anti-IL-33 therapy during hepatectomy might reduce the risk of CCA recurrence.

IIAEK Targets Intestinal Alkaline Phosphatase (IAP) to Improve Cholesterol Metabolism with a Specific Activation of IAP and Downregulation of ABCA1.

IIAEK (Ile-Ile-Ala-Glu-Lys, lactostatin) is a novel cholesterol-lowering pentapeptide derived from bovine milk ß-lactoglobulin. However, the molecular mechanisms underlying the IIAEK-mediated suppression of intestinal cholesterol absorption are unknown. Therefore, we evaluated the effects of IIAEK on intestinal cholesterol metabolism in a human intestinal model using Caco-2 cells. We found that IIAEK significantly reduced the expression of intestinal cholesterol metabolism-associated genes, particularly that of the ATP-binding cassette transporter A1 (ABCA1). Subsequently, we chemically synthesized a novel molecular probe, IIXEK, which can visualize a complex of target proteins interacting with photoaffinity-labeled IIAEK by fluorescent substances. Through photoaffinity labeling and MS analysis with IIXEK for the rat small intestinal mucosa and intestinal lipid raft fractions of Caco-2 cells, we identified intestinal alkaline phosphatase (IAP) as a specific molecule interacting with IIAEK and discovered the common IIAEK-binding amino acid sequence, GFYLFVEGGR. IIAEK significantly increased IAP mRNA and protein levels while decreasing ABCA1 mRNA and protein levels in Caco-2 cells. In conclusion, we found that IIAEK targets IAP to improve cholesterol metabolism via a novel signaling pathway involving the specific activation of IAP and downregulation of intestinal ABCA1.

Single-incision retroperitoneal laparoscopic repair of superior lumbar hernia using self-fixating ProGrip mesh: A case report.

INTRODUCTION: Lumbar hernia is rare and represents less than 1-2% of all abdominal hernias. There are mainly two types of lumbar hernia: superior lumbar hernia and inferior lumbar hernia. CASE PRESENTATION: A 65-year-old woman was admitted complaining of a mass in her left lumbar area. Under a diagnosis of superior lumbar hernia, single-incision laparoscopic retroperitoneal repair was performed. A single, 2-cm-long incision was made and the retroperitoneal space was dissected gradually. The hernia orifice was recognized and hernia sac was slipped from the hernia orifice. The collateral branch of subcostal nerve and iliohypogastric nerve were recognized. Laparoscopic self-fixating mesh was placed to cover the hernia orifice without mesh fixation. The patient remained well with no signs of recurrence. DISCUSSION: In laparoscopic lumbar hernia repair, it is important to be careful not to damage subcostal nerve and iliohypogastric nerve. Self-fixating mesh without fixation is useful due to the prevention from nerve injury. To our best knowledge, this is the first report of single-incision laparoscopic repair for superior lumbar hernia. Single-incision laparoscopic surgery could provide good cosmetic results with minimal incision. CONCLUSION: We successfully performed single-incision retroperitoneal laparoscopic repair of superior lumbar hernia using self-fixating mesh.

Epigallocatechin Gallate Induces Upregulation of LDL Receptor via the 67 kDa Laminin Receptor-Independent Pathway in HepG2 Cells.

SCOPE: Epigallocatechin gallate (EGCG), an active polyphenol in green tea, exhibits various physiological effects, including activation of low-density lipoprotein receptors (LDLR). The previous studies have suggested that EGCG activates LDLR via extracellular signal-regulated kinase (ERK) pathway in HepG2 cells. However, the detailed molecular mechanism remains unclear. Recently, 67 kDa laminin receptor (67LR) is identified as a receptor for EGCG. Therefore, this study aims to determine whether 67LR is involved in the mechanism of LDLR activation by EGCG. METHODS AND RESULTS: EGCG induces upregulation of LDLR when 67LR is knocked down in HepG2 cells. Similar effect is observed after the cells are treated with 67LR monoclonal antibody. The loss of antiallergic effect following 67LR siRNA knockdown and 67LR antibody treatment confirms the results since the antiallergic effect of EGCG is known to be mediated by 67LR. CONCLUSION: EGCG activates LDLR expression via 67LR-independent pathway in HepG2 cells.

Identification of a novel cholesterol-lowering dipeptide, phenylalanine-proline (FP), and its down-regulation of intestinal ABCA1 in hypercholesterolemic rats and Caco-2 cells.

There has been no report about in vivo active cholesterol-lowering dipeptide in any protein origin, despite their potential health benefits. Cattle heart protein hydrolysate ultra-filtrate (HPHU, molecular weight < ca. 1,000 Da peptide mixture) exhibits cholesterol-lowering activity in hypercholesterolemic rats, but the active peptide in HPHU that lowers serum cholesterol levels and its molecular mechanism are unknown. In this study, we separated and purified HPHU to identify a novel cholesterol-lowering dipeptide (phenylalanine-proline, FP) and characterized the mechanism underlying its effects in vivo and in vitro. We identified FP as an active peptide from HPHU by MALDI-TOF mass spectrometry. FP significantly decreased serum total and non-HDL cholesterol and hepatic cholesterol levels in rats. FP significantly increased serum HDL cholesterol, accompanied by a significant decrease in the atherogenic index. FP also significantly increased fecal cholesterol and acidic steroid excretion. Moreover, FP significantly decreased ATP-binding cassette transporter A1 (ABCA1) expression in the rat jejunum and reduced cholesterol absorption in Caco-2 cells. We found a novel cholesterol-lowering dipeptide FP that could improve cholesterol metabolism via the down-regulation of intestinal ABCA1. The cholesterol-lowering action induced by FP was disappeared in PepT1KO mice. FP-induced cholesterol-lowering action is mediated via PepT1 in mice.