富含 DHA 的鱼油上调细胞周期蛋白依赖性激酶抑制剂 2A（P16）的表达，下调端粒酶活性，而不调节 2 型糖尿病患者 PPARγ Pro12Ala 多态性的作用：一项随机、双盲、安慰剂对照的临床试验。
DHA-enriched fish oil upregulates cyclin-dependent kinase inhibitor 2A (P16) expression and downregulates telomerase activity without modulating effects of PPARγ Pro12Ala polymorphism in type 2 diabetic patients: A randomized, double-blind, placebo-controlled clinical trial.
机构信息
Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
出版信息
Clin Nutr. 2018 Feb;37(1):91-98. doi: 10.1016/j.clnu.2016.12.007. Epub 2016 Dec 19.
OBJECTIVE
The present study investigated the effects of docosahexaenoic acid (DHA)-enriched fish oil supplement on telomerase activity, mRNA expression of P16, IL-6, and TNF-α considering Pro12Ala polymorphism in the PPARγ gene.
METHODS/DESIGN: In this double-blind randomized controlled trial, 72 PPARγ Pro12Ala polymorphism genotyped type 2 diabetic patients aged 30-70 years were randomly assigned to receive 2.4 gr of DHA-enriched fish oil or a placebo for 8 weeks. Genotyping of the Pro12Ala polymorphism in the PPARγ gene was assessed using polymerase chain reaction-restriction length polymorphism (PCR-RFLP), telomerase activity in the peripheral blood mononuclear cell (PBMC) was measured using PCR-ELISA based on the telomeric repeat amplification protocol (TRAP), and changes in the mRNA expression of P16, IL-6, and TNF-α were measured using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR).
RESULTS
In the DHA group, telomerase activity was decreased (p = 0.001) during the intervention. In addition, between-group comparisons showed significant differences in the changes in telomerase activity (p = 0.003) and P16 mRNA expression (p = 0.028) and non-significant differences in TNF-α and IL-6 mRNA expression. The gene*DHA interaction could not affect changes in P16, IL-6, or TNF-α mRNA expression or in telomerase activity in PBMC.
DISCUSSION
Short-time DHA-enriched fish oil supplementation caused increased levels of P16 expression and a decline in telomerase activity compared with the control group without modulating the effects of Pro12Ala polymorphism on the PPARγ gene. Because of the positive correlation between P16 activity and cellular senescence, the possibility of senescence stimulation by DHA is proposed.
目的
本研究旨在探讨富含二十二碳六烯酸（DHA）的鱼油补充剂对端粒酶活性、P16、IL-6 和 TNF-αmRNA 表达的影响，同时考虑过氧化物酶体增殖物激活受体γ（PPARγ）基因 Pro12Ala 多态性。
方法/设计：在这项双盲随机对照试验中，将 72 名年龄在 30-70 岁之间、PPARγ Pro12Ala 多态性基因型为 2 型糖尿病患者随机分为两组，分别接受 2.4 克 DHA 强化鱼油或安慰剂治疗 8 周。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测 PPARγ 基因 Pro12Ala 多态性，外周血单个核细胞（PBMC）端粒酶活性采用基于端粒重复扩增协议（TRAP）的 PCR-ELISA 检测，P16、IL-6 和 TNF-αmRNA 表达变化采用实时定量逆转录聚合酶链反应（RT-PCR）检测。
结果
在 DHA 组，干预期间端粒酶活性降低（p=0.001）。此外，组间比较显示端粒酶活性变化（p=0.003）和 P16mRNA 表达变化（p=0.028）存在显著差异，而 TNF-α和 IL-6mRNA 表达变化无显著差异。基因*DHA 相互作用不能影响 PBMC 中 P16、IL-6 或 TNF-αmRNA 表达或端粒酶活性的变化。
讨论
短期 DHA 强化鱼油补充剂与对照组相比，导致 P16 表达水平升高和端粒酶活性下降，但对 PPARγ 基因 Pro12Ala 多态性的影响没有调节作用。由于 P16 活性与细胞衰老之间存在正相关，因此提出 DHA 可能刺激衰老的可能性。
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