Hernando-Redondo Javier, Hernáez Álvaro, Sanllorente Albert, Pintó Xavier, Estruch Ramón, Salas-Salvadó Jordi, Corella Dolores, Arós Fernando, Martínez-González Miguel Ángel, Subirana Isaac, Muñoz-Aguayo Daniel, Malcampo Mireia, Serra-Majem Lluis, Romaguera Dora, Lapetra Jose, Ros Emilio, Tinahones Francisco, Lamuela-Raventós Rosa Maria, Gómez-Gracia Enrique, Fitó Montserrat, Castañer Olga
Consorcio CIBER, Pathophysiology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.
Unit of Cardiovascular Risk and Nutrition, Hospital del Mar Medical Research Institute, Barcelona, Spain.
Mol Nutr Food Res. 2025 Jul;69(13):e70050. doi: 10.1002/mnfr.70050. Epub 2025 May 9.
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 (ABCA1), retinoid X receptor alpha (RXRA), retinoid X receptor beta (RXRB), and Nuclear Receptor Subfamily 1 Group H Member 3 (NR1H3) was observed in response to MedDiet-EVOO, MedDiet-Nuts, and Er-MedDiet. Notably, RXRA expression was higher in both MedDiet-EVOO and MedDiet-Nuts compared to the control diet. Differences in gene expression, particularly RXRA, ATP binding cassette subfamily G member 1 (ABCG1), NR1H3, and Peroxisome Proliferator Activated Receptor Delta (PPARD), 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 RXRA, RXRB, ABCA1, ABCG1, Nuclear Receptor Subfamily 1 Group H Member 2(NR1H2), and PPARD-among elderly adults at high cardiovascular risk. This suggests a potential mechanism by which these diets may exert cardiovascular protective effects.
在本研究中，我们调查了接受地中海饮食干预的心血管高风险个体中与胆固醇流出受体相关的基因表达。通过转录组分析，我们检测了来自两项随机对照试验（PREDIMED和PREDIMED-Plus）的样本，分别有151名和89名老年人。在基线和12个月干预后分离血细胞。在PREDIMED试验中，参与者遵循不同的地中海饮食：一种补充特级初榨橄榄油（富含特级初榨橄榄油的传统地中海饮食[MedDiet-EVOO]），另一种补充坚果（富含坚果的地中海饮食[MedDiet-Nuts]），以及低脂对照饮食。PREDIMED-Plus试验将能量减少的地中海饮食（Er-MedDiet）加体育活动与随意的地中海饮食进行了比较。随着时间的推移，观察到在响应MedDiet-EVOO、MedDiet-Nuts和Er-MedDiet时，ATP结合盒亚家族A成员1（ABCA1）、视黄酸X受体α（RXRA）、视黄酸X受体β（RXRB）和核受体亚家族1组H成员3（NR1H3）等基因出现轻度但显著的上调。值得注意的是，与对照饮食相比，MedDiet-EVOO和MedDiet-Nuts中RXRA的表达均更高。MedDiet-Nuts与对照饮食之间在基因表达上存在差异，特别是RXRA、ATP结合盒亚家族G成员1（ABCG1）、NR1H3和过氧化物酶体增殖物激活受体δ（PPARD）。在PREDIMED-Plus试验中，饮食组之间未发现基因表达有显著差异。主成分分析（PCA）和线性判别分析（LDA）显示不同地中海饮食干预的基因表达谱存在重叠。总之，我们的研究强调了长期坚持地中海饮食（无论热量正常还是热量减少）对心血管健康的益处，主要表现为心血管高风险老年人中胆固醇流出相关基因（特别是涉及RXRA、RXRB、ABCA1、ABCG1、核受体亚家族1组H成员2（NR1H2）和PPARD）的轻度上调。这提示了这些饮食可能发挥心血管保护作用的潜在机制。
