Molecular Nutrition & Food Research最新文献

{"title":"Proteomic Profiling Informs Mechanisms of Esophageal Adenocarcinoma Inhibition by Cranberry Proanthocyanidins.","authors":"Yun Zhang,Michelle Lee,Erika de Jesus,Katherine Weh,Connor Howard,Henriette Remmer,Amy B Howell,Laura A Kresty","doi":"10.1002/mnfr.70102","DOIUrl":"https://doi.org/10.1002/mnfr.70102","url":null,"abstract":"Cranberry proanthocyanidins (CPACs) exert potent antiinflammatory and antibacterial activities in humans and anticancer effects in preclinical models, including those targeting esophageal adenocarcinoma (EAC). This study applied proteomic profiling to investigate CPACs' inhibitory effects on reflux-induced EAC in a rat model. Tandem mass spectrometry was applied to protein isolated from water-, CPAC-, and reflux-exposed esophagi with and without CPAC treatment. Differentially expressed proteins were identified, followed by enrichment analyses to assess CPACs' capacity to ameliorate reflux-induced changes in gene set hallmarks, pathways, and process networks. CPAC directly reversed 42.1% of reflux-induced protein alterations. Gene set enrichment analysis (GSEA) revealed CPAC mitigated 11 hallmarks enriched in reflux-induced EAC (i.e., oxidative phosphorylation, myogenesis, adipogenesis, MYC targets, and P53). Top pathways over-represented with reflux and directly reversed by CPAC included spliceosome, metabolic pathways, and IL-17 signaling. Transcription_mRNA processing, translation_regulation/initiation, and inflammation (i.e., kallikrein-kinin system, neutrophil activation) dominated process networks upregulated by reflux and downregulated by CPAC. Networks exclusively altered by reflux and not mitigated by CPAC included ribosomal-linked translation, immune response_antigen presentation, and leptin signaling. Similarly, CPAC did not reverse the reflux-linked downregulation of ubiquinone metabolism. Identifying reflux-induced cancer processes and pathways that CPAC fails to mitigate may inform opportunities for combination prevention efforts moving forward.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"19 1","pages":"e70102"},"PeriodicalIF":5.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telomeres and Telomerase: Targets for Chemoprevention of Hepatocellular Carcinoma With Bioactive Food Compounds.","authors":"Juliana Marques Affonso,Thais Pereira D'Amico,Maria Aderuza Horst,Fernando Salvador Moreno,Renato Heidor","doi":"10.1002/mnfr.70088","DOIUrl":"https://doi.org/10.1002/mnfr.70088","url":null,"abstract":"The maintenance of telomere length by telomerase plays an essential role in senescence, aging, and cancer. Mutations in the TERT promoter, a telomerase subunit, are frequent in human cancers. In hepatocellular carcinoma (HCC), telomere shortening contributes to preneoplastic conditions such as cirrhosis. Telomerase activation during cirrhosis may reduce chromosomal instability, while its suppression in early dysplastic nodules may prevent hepatocarcinogenesis. Evidence suggests that bioactive food compounds (BFCs) can reduce the incidence and/or delay the onset of HCC by modulating telomerase activity. A systematic review was conducted on the role of BFCs in telomerase activity during hepatocarcinogenesis. BFCs were analyzed in isolated form or as part of extracts and categorized into fatty acids, isoprenoids, isothiocyanates, and phenolic compounds. Despite structural diversity, BFCs modulate telomerase through common mechanisms, including inhibition of activating proteins at the TERT promoter, activation of nuclear receptors, or histone H3 hyperacetylation. Indirectly, telomerase can also be modulated via activation of antioxidant defense pathways. Understanding telomerase reactivation and its modulation by BFCs is key to establishing effective HCC chemoprevention strategies targeting telomerase.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"3 1","pages":"e70088"},"PeriodicalIF":5.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Delivery of Ellagic Acid Encapsulated in Milk Exosomes: Sex-Based Differences in Bioavailability, Urolithin Production, and Gut Microbiota Modulation.","authors":"María Ángeles Ávila-Gálvez,María Romo-Vaquero,Carmen Mazarío-Gárgoles,Joao Tomé-Carneiro,María-Carmen López de Las Hazas,Alberto Dávalos,María Victoria Selma,Antonio González-Sarrías,Juan Carlos Espín","doi":"10.1002/mnfr.70104","DOIUrl":"https://doi.org/10.1002/mnfr.70104","url":null,"abstract":"Milk exosomes (EXOs) enhance polyphenols' bioavailability, but their potential for oral administration remains underexplored. Ellagic acid (EA) is poorly bioavailable. We investigate whether EA encapsulated in EXOs (EXO-EA) consumed orally improves EA bioavailability and (or) modulates gut microbiota. For 2 weeks, BALB/c mice received EXO, non-encapsulated EA (NEA), or EXO-EA (0.27 mg EA/kg bw) orally. Targeted and untargeted metabolomics (UPLC-qTOF-MS), fecal SCFAs (GC-MS), and gut microbiota (PacBio 16S-sequencing) were performed. Additionally, EA plasma and brain kinetics were evaluated in rats following intravenous administration of EXO-EA and NEA. Unlike NEA, EXO-EA quadrupled EA plasma levels in Sprague-Dawley rats and enabled brain detection. However, oral EXO-EA in mice failed to deliver EA systemically due to gastrointestinal instability, confirmed by in vitro digestion. Sex-dependent EXO-EA metabolomic effects were observed. Also, in males only, EXO-EA increased fecal urolithin A and SCFAs and enriched the microbiota with Christensenellaceae R7, Ruminococcus species, and Clostridium fusiformis, among others. In females, both EXO-EA and NEA enriched the microbiota with bifidobacteria, including Bifidobacterium pseudolongum. Oral EXO-EA impacted plasma metabolome, modulated gut microbiota, and increased urolithin A and SCFA production sex-dependently. However, gastrointestinal instability, limited EA encapsulation, and low dose administered prevented systemic delivery.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"7 1","pages":"e70104"},"PeriodicalIF":5.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tibetan Tea Alleviates the Intestinal Dysfunction in Sleep-Deprived Mice Through Regulating Oxidative Stress and Inflammation-Related Intestinal Metabolisms.","authors":"Ge Liang,Wen Zheng,Yaru Dai,Yijin Li,Xinyi Hu,Lu Zhang,Luolan Gui,Qian Ran,Yi Zhong,Shisheng Wang,Tao Su,Dingkun Zhang,Chao Li,Chaogui Li,Digang Zhou,Peng Li,Meng Gong","doi":"10.1002/mnfr.70098","DOIUrl":"https://doi.org/10.1002/mnfr.70098","url":null,"abstract":"Sleep deprivation (SD) disrupts intestinal homeostasis through excessive reactive oxygen species (ROS) accumulation. Tibetan tea is a potential dietary intervention for inflammation, it's effect on SD-induced intestinal inflammation remains unclear. This study investigates the alleviating effects of Tibetan tea water-soluble extract (TTE) on intestinal dysfunction in SD mice. After TTE supplementation, the physiological activity, inflammatory cytokines, and oxidative stress levels were assessed in SD-induced intestinal dysfunction mice. SD increased ROS levels and pro-inflammatory cytokines in plasma and small intestine, causing intestinal injury characterized by reduced goblet cells, decreased Mucin2 (MUC2) expression, and impaired tight junction proteins. Conversely, TTE reversed these disorders and improved mucosal injury in the small intestine. Furthermore, TTE modulated gut microbiota by enriching probiotics linked to SCFA production and restored SD-induced metabolic disturbances in the small intestine and systemic circulation, particularly affecting tricarboxylic acid (TCA) cycle, urea cycle, and TAG-related metabolites. Overall, TTE remarkably ameliorated SD-induced intestinal dysfunction through reducing ROS, restoring intestinal barrier function, and regulating the gut microbiome, which suggested that Tibetan tea could contribute to the treatment of intestinal inflammation.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"96 1","pages":"e70098"},"PeriodicalIF":5.2,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol Enhances CAR NK Cell Function in Cellular Immunotherapy of Non-Hodgkin Lymphoma.","authors":"Xuanren Shi,Xiaoqing Wu,Feng Yang,Xiaofang Hu,Qingzheng Kang","doi":"10.1002/mnfr.70112","DOIUrl":"https://doi.org/10.1002/mnfr.70112","url":null,"abstract":"Resveratrol (RSV) is a dietary polyphenolic compound with anticancer property. However, its clinical translation as an anticancer chemotherapeutic agent is hindered by multiple challenges. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy has emerged as a promising immunotherapeutic strategy against refractory malignancies. The role of RSV in CAR NK cell therapy remains unexplored. This study pioneers the investigation of RSV's role in CAR NK immunotherapy. Specially, RSV preconditioning improved CAR NK cells' resistance to oxidative stress, and augmented energetic metabolism in CAR NK cells. More importantly, the enhanced cytotoxicity against cancer cells of non-Hodgkin lymphoma (NHL) and stronger cytokine secretions were observed in RSV-treated anti-CD19 CAR NK cells. In vivo tracking revealed RSV extended CAR NK tissue residency and enhanced therapeutic efficacy in NHL xenografts. RSV-adjuvanted anti-CD19 CAR NK therapy achieved an obvious reduction in intraperitoneal tumor burden and improvement in the mice survival. Our mechanistic investigation revealed that nuclear factor erythroid 2-related factor 2 (NRF2) serves as a critical mediator in RSV-induced functional augmentation of CAR NK cells. These findings established RSV as a potential polyphenol adjuvant capable of improving CAR NK therapy, providing a translatable strategy for polyphenols to overcome current limitations in cancer therapy.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"26 1","pages":"e70112"},"PeriodicalIF":5.2,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of Ginger Oil to Prevent 4‐(Methylnitrosamino)‐1‐(3‐Pyridyl)‐1‐Butanone‐Induced Lung Cancer Through Gut Microbiota Modulation and Inflammatory Response Inhibition","authors":"Yan Ding, Lei Zhang, Wenli Zhao, Tianyuan Wang, Ying Shi, Chunlin Zhuang, Zhuo Qu","doi":"10.1002/mnfr.70103","DOIUrl":"https://doi.org/10.1002/mnfr.70103","url":null,"abstract":"Lung cancer remains the leading cause of cancer‐related mortality worldwide, with tobacco carcinogens such as 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) playing a central role in its pathogenesis. Chemoprevention through dietary or natural compounds offers a promising strategy to mitigate cancer risk. Published studies have indicated that ginger oil (GIO), a bioactive extract from ginger, possesses various bioactivities, suggesting its potential for cancer chemopreventive. In this study, we aimed to investigate the lung cancer chemopreventive potential of GIO. An NNK‐induced lung cancer model in A/J mice was utilized to evaluate the preventive effect of GIO against lung cancer. Additionally, the potential mechanisms by which GIO might prevent NNK‐induced lung cancer were assessed using molecular biology techniques combined with multi‐omics. The results demonstrated that GIO decreased the number of lung tumors in the lungs of mice. Mechanistically, GIO exerts chemopreventive effects by modulating both the TLR4/NF‐κB and PPARγ/NF‐κB signaling axes, thereby suppressing downstream pro‐inflammatory mediators. Furthermore, GIO modulates gut microbiota composition and its metabolites. Critically, its lung chemopreventive efficacy against NNK‐induced lung carcinogenesis is partially dependent on microbiota‐mediated regulation. Overall, these findings underscore the nutritional value of GIO as a diet‐derived chemopreventive agent against lung cancer caused by tobacco carcinogens.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"290 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Soybean-Derived Bioactive Components in Prevention and Intervention of Lung Cancer","authors":"Tianzhu Guan, Xiaoxiao Liu, Longfei Zhang, Chenxi Ren, Yining Feng, Zhenquan Yang, Lixia Xiao","doi":"10.1002/mnfr.70105","DOIUrl":"https://doi.org/10.1002/mnfr.70105","url":null,"abstract":"Soybean (<i>Glycine max</i>) is one of Asia's most valuable oil crops, offering a rich source of dietary protein and bioactive compounds with diverse clinical applications. Key bioactive phytochemicals in soybean, including isoflavones, flavonoids, carotenoids, phytosterols, soyasaponins, fatty acids, and protein isolates, are known for their potential health benefits. These compounds exert functional properties by modulating critical metabolic pathways, such as the mitogen-activated protein kinase (MAPK), estrogen receptor (ER), and nuclear factor kappa-B (NF-κB) pathways. With a growing body of epidemiological and clinical evidence supporting the anticancer potential of soybean, this review systematically examines the role of soybean-derived bioactive components in the prevention and treatment of lung cancer. To our knowledge, this is the first review to focus specifically on the impact of soy-derived bioactive components on lung cancer progression and modulation, offering insights into their mechanisms and potential as dietary interventions.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"49 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Effects of Wild Blueberry (Poly)Phenol Metabolites in Modulating Lipid Metabolism and Oxidative Stress in 3T3-L1 Adipocytes","authors":"Samuele Venturi, Marco Rendine, Mirko Marino, Dorothy Klimis-Zacas, Patrizia Riso, Cristian Del Bo'","doi":"10.1002/mnfr.70101","DOIUrl":"https://doi.org/10.1002/mnfr.70101","url":null,"abstract":"Adipocyte hypertrophy, driven by lipid accumulation, is crucial in the development of obesity. Wild blueberry (WB; <i>Vaccinium angustifolium</i>) (poly)phenols (PPs) metabolites may modulate adipogenesis and the development of obesity. This study examines WB PP metabolites’ effects on lipid accumulation, lipid metabolism, and oxidative stress in mature 3T3-L1 adipocytes. Differentiated 3T3-L1 adipocytes were treated for 48 h with free fatty acids (FFAs; oleic/palmitic acid 750 µM, 2:1 ratio) and WB-derived PPs, including ferulic acid (FA), isoferulic acid (IA), vanillic acid (VA), and syringic acid (SA) at physiological and supra-physiological concentrations. Assessments included lipid accumulation, glycerol release, and markers of lipid metabolism (sterol regulatory element-binding protein 1c [SREBP-1], fatty acid synthase [FASN], FAB4) and oxidative stress (DNA damage, 8-hydroxy 2-deoxyguanosine [8OHdG], nuclear erythroid factor 2-related factors 2 (NRF2), heme oxygenase 1 [HO-1]). FFAs significantly increased lipid accumulation, glycerol release, and FASN levels, while reducing HO-1 levels, without affecting other markers. WB PP metabolites did not reduce lipid accumulation, but IA and VA reduced FASN levels (−25% and −26%; <i>p</i> &lt; 0.05), and SA improved HO-1 levels (+150%; <i>p</i> &lt; 0.05). Despite the different effects observed, the findings obtained under our experimental conditions seem to suggest that IA, VA, and SA may modulate lipid metabolism and oxidative stress markers. However, further studies are fundamental to corroborate the findings obtained and support the contribution of these BB PPs metabolites and other compounds in the prevention and management of obesity.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"25 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yarrow (Achillea millefolium) Extract Modulates the Gut Microbiota Composition and Activity in the TIM-2 In Vitro Model of the Colon","authors":"Ana Bačić, Kahlile Youssef Abboud, Yanyun Zhang, Mirjana Rajilić-Stojanović","doi":"10.1002/mnfr.70074","DOIUrl":"https://doi.org/10.1002/mnfr.70074","url":null,"abstract":"Phenolic compounds, abundantly found in medicinal herbs, may promote health by modulating the gut microbiota. Yarrow is a traditional remedy for digestive and non-gastrointestinal diseases with unexplored interaction with gut microbes. This study aimed to evaluate the effects of yarrow extract and a phenolic mixture comprising apigenin, caffeic, and chlorogenic acids on the gut microbiota using the TIM-2 in vitro system. The TIM-2 units were inoculated with fecal samples from healthy individuals and supplemented with test substrates for 72 h. Microbiota composition was assessed by V₃-V₄ 16S rRNA gene sequencing, while organic acid production was evaluated by GC-MS. The yarrow extract stimulated probiotic bacteria <i>Lactiplantibacillus</i>, and other abundant and symbiotic gut inhabitants, including Eggerthellaceae, Christensenellaceae, Butyricicoccaceae, and the <i>Eubacterium coprostanoligenes</i> group. The phenolic mixture exerted milder effects on gut microbiota by enhancing the growth of Eggerthellaceae and <i>Collinsella</i>. Looking at the microbial activity, the production of SCFAs, specifically acetic and propionic acids, was increased in the yarrow group. The obtained results highlight the importance of yarrow phenolics in maintaining microbiota balance. The yarrow extract and specific phenolics may modulate the gut microbiota by promoting the growth of SCFA producers and stimulating SCFA synthesis.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"26 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mediterranean Diet Modulates Gene Expression of Cholesterol Efflux Receptors in High-Risk Cardiovascular Patients","authors":"Javier Hernando-Redondo, Álvaro Hernáez, Albert Sanllorente, Xavier Pintó, Ramón Estruch, Jordi Salas-Salvadó, Dolores Corella, Fernando Arós, Miguel Ángel Martínez-González, Isaac Subirana, Daniel Muñoz-Aguayo, Mireia Malcampo, Lluis Serra-Majem, Dora Romaguera, Jose Lapetra, Emilio Ros, Francisco Tinahones, Rosa Maria Lamuela-Raventós, Enrique Gómez-Gracia, Montserrat Fitó, Olga Castañer","doi":"10.1002/mnfr.70050","DOIUrl":"https://doi.org/10.1002/mnfr.70050","url":null,"abstract":"In this study, we investigated gene expression related to cholesterol efflux receptors in individuals at high cardiovascular risk undergoing Mediterranean dietary interventions. Through transcriptomic analysis, we examined samples from two randomized controlled trials: PREDIMED and PREDIMED-Plus, with 151 and 89 elderly adults, respectively. Blood cells were isolated at baseline and after a 12-month intervention. In the PREDIMED trial, participants followed different Mediterranean diets: one supplemented with extra-virgin olive oil (traditional Mediterranean diet enriched with extra-virgin olive oil [MedDiet-EVOO]), another with nuts (MedDiet enriched with nuts MedDiet-Nuts [MedDiet-Nuts]), and a low-fat control diet. The PREDIMED-Plus trial compared an energy-reduced Mediterranean diet (Er-MedDiet) with physical activity to an ad libitum Mediterranean diet. Over time, mild but significant upregulation of genes like ATP binding cassette subfamily A member 1 (<i>ABCA1</i>), retinoid X receptor alpha (<i>RXRA</i>), retinoid X receptor beta (<i>RXRB</i>), and <i>Nuclear Receptor Subfamily 1 Group H Member 3 (NR1H3)</i> was observed in response to MedDiet-EVOO, MedDiet-Nuts, and Er-MedDiet. Notably, <i>RXRA</i> expression was higher in both MedDiet-EVOO and MedDiet-Nuts compared to the control diet. Differences in gene expression, particularly <i>RXRA</i>, ATP binding cassette subfamily G member 1 (<i>ABCG1</i>), <i>NR1H3</i>, and <i>Peroxisome Proliferator Activated Receptor Delta (PPARD)</i>, were evident between MedDiet-Nuts and the control diet. In the PREDIMED-Plus trial, no significant differences in gene expression were found between dietary groups. Principal component analysis (PCA) and linear discriminant analysis (LDA) showed overlapping gene expression profiles across different Mediterranean diet interventions. In conclusion, our study highlights the cardiovascular health benefits of long-term adherence to a Mediterranean diet, both normocaloric and hypocaloric, primarily reflected by mild upregulation of cholesterol efflux-related genes—specifically involving <i>RXRA</i>, <i>RXRB</i>, <i>ABCA1</i>, <i>ABCG1</i>, <i>Nuclear Receptor Subfamily 1 Group H Member 2(NR1H2)</i>, and <i>PPARD</i>—among elderly adults at high cardiovascular risk. This suggests a potential mechanism by which these diets may exert cardiovascular protective effects.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"39 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}