Laboratory of Epigenetics of Lipid Metabolism, Instituto Madrileño de Estudios Avanzados (IMDEA)-Alimentación, CEI UAM + CSIC, 28049 Madrid, Spain.
Lipid Clinic, Endocrinology and Nutrition Service, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, 08036 Barcelona, Spain.
Nutrients. 2022 Apr 1;14(7):1473. doi: 10.3390/nu14071473.
The mechanisms underlying the lipid-lowering effect of nuts remain elusive. This study explores whether one-year supplementation with walnuts decreases LDL-cholesterol (LDL-C) by affecting the expression of circulating microRNAs (c-miRNA). In this sub-study of the Walnuts and Healthy Aging (WAHA) trial, we obtained fasting serum at baseline and at 1 year from 330 free-living participants (63-79 year, 68% women), allocated into a control group (CG, abstinence from walnuts, = 164) and a walnut group (WG, 15% of daily energy as walnuts, ~30-60 g/d, = 166). Participants in the WG showed a 1 year decrease in LDL-C (-9.07, (95% confidence interval: -12.87; -5.73) mg/dL; = 0.010 versus changes in the CG). We conducted a miRNA array in eight randomly selected participants in the WG who decreased in LDL-C. This yielded 53 c-miRNAs with statistically significant changes, 27 of which survived the correction for multiple testing. When validating them in the full population, statistical significance lasted for hsa-miR-551a, being upregulated in the WG. In mediation analysis, the change in hsa-miR-551a was unrelated to LDL-C decrease. Long-term supplementation with walnuts decreased LDL-C independently of the changes in c-miRNA. The hsa-miR-551a upregulation, which has been linked to a reduced cell migration and invasion in several carcinomas, suggests a novel mechanism of walnuts in cancer risk.
坚果降低血脂的作用机制仍不清楚。本研究探讨了一年期的核桃补充是否通过影响循环 microRNA (c-miRNA) 的表达来降低 LDL-胆固醇 (LDL-C)。在 Walnuts and Healthy Aging (WAHA) 试验的子研究中，我们从 330 名自由生活的参与者（63-79 岁，68%为女性）中获得了基线和 1 年的空腹血清，将其分为对照组 (CG，避免食用核桃，n = 164) 和核桃组 (WG，每天能量的 15%作为核桃，~30-60 g/d，n = 166)。WG 组的 LDL-C 在 1 年内下降（-9.07，(95%置信区间：-12.87；-5.73)mg/dL；=0.010 与 CG 相比变化）。我们在 8 名 LDL-C 降低的 WG 中随机选择了参与者进行 miRNA 阵列分析。这产生了 53 个具有统计学意义变化的 c-miRNA，其中 27 个在经过多重检验校正后仍然存在。在全人群中验证时，hsa-miR-551a 的统计学意义持续存在，在 WG 中上调。在中介分析中，hsa-miR-551a 的变化与 LDL-C 降低无关。长期补充核桃可独立于 c-miRNA 的变化降低 LDL-C。hsa-miR-551a 的上调与几种癌中的细胞迁移和侵袭减少有关，提示了核桃在癌症风险中的一种新机制。
