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采用全基因组基因表达方法,增加蛋白质摄入量会影响居家老年受试者外周血单核细胞中阿黑皮素原(POMC)的加工、免疫功能和胰岛素样生长因子(IGF)信号传导。

Increased protein intake affects pro-opiomelanocortin (POMC) processing, immune function and IGF signaling in peripheral blood mononuclear cells of home-dwelling old subjects using a genome-wide gene expression approach.

作者信息

Gjevestad Gyrd O, Holven Kirsten B, Rundblad Amanda, Flatberg Arnar, Myhrstad Mari, Karlsen Karina, Mutt Shivaprakash J, Herzig Karl-Heinz, Ottestad Inger, Ulven Stine M

机构信息

1Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1046, Blindern, 0317 Oslo, Norway.

2Innovation and marketing, TINE SA, Lakkegata 23, 0187 Oslo, Norway.

出版信息

Genes Nutr. 2019 Nov 28;14:32. doi: 10.1186/s12263-019-0654-6. eCollection 2019.

DOI:10.1186/s12263-019-0654-6
PMID:31798754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6883584/
Abstract

BACKGROUND

Adequate protein intake among older adults is associated with better health outcomes such as immune function and metabolic regulation of skeletal muscle, but conflicting results make it difficult to define the optimal intake. To further understand the impact of protein intake on metabolic processes, the aim of the study was to explore genome-wide gene expression changes in peripheral blood mononuclear cells (PBMCs) in home-dwelling old subjects after increased protein intake for 12 weeks.

METHOD

In a parallel double-blind randomized controlled intervention study, subjects (≥ 70 years) received a protein-enriched milk (2 × 20 g protein/day, = 14, mean (±SD) age 76.9 ± 4.9 years) or an isocaloric carbohydrate drink ( = 17, mean (±SD) age 77.7 ± 4.8 years) for breakfast and evening meal for 12 weeks. PBMCs were isolated before and after the intervention. Microarray analysis was performed using Illumina technology. Serum levels of gut peptides and insulin growth factor (IGF)-1 were also measured.

RESULTS

In total 758 gene transcripts were regulated after increased protein intake, and 649 gene transcripts were regulated after intake of carbohydrates ( < 0.05). Forty-two of these genes were overlapping. After adjusting for multiple testing, 27 of the 758 gene transcripts were regulated (FDR, -value < 0.25) after protein intake. Of these 25 were upregulated and two downregulated. In particular, genes and signaling pathways involved in pro-opiomelanocortin (POMC) processing, immune function, and IGF signaling were significantly altered.

CONCLUSIONS

PBMCs can be used to study gene expression changes after long-term protein intake, as many signaling pathways were regulated after increased protein intake. The functional significance of these findings needs to be further investigated.

TRIAL REGISTRATION

ClinicalTrials.gov, ID no. NCT02218333. The study was registered on August 18, 2014.

摘要

背景

老年人摄入足够的蛋白质与更好的健康结果相关,如免疫功能和骨骼肌的代谢调节,但相互矛盾的结果使得难以确定最佳摄入量。为了进一步了解蛋白质摄入对代谢过程的影响,本研究的目的是探讨居家老年受试者在蛋白质摄入量增加12周后外周血单核细胞(PBMC)全基因组基因表达的变化。

方法

在一项平行双盲随机对照干预研究中,受试者(≥70岁)早餐和晚餐分别接受富含蛋白质的牛奶(2×20g蛋白质/天,n = 14,平均(±标准差)年龄76.9±4.9岁)或等热量碳水化合物饮料(n = 17,平均(±标准差)年龄77.7±4.8岁),持续12周。在干预前后分离PBMC。使用Illumina技术进行微阵列分析。还测量了肠道肽和胰岛素生长因子(IGF)-1的血清水平。

结果

蛋白质摄入量增加后,共有758个基因转录本受到调节,碳水化合物摄入后有649个基因转录本受到调节(P < 0.05)。其中42个基因重叠。在进行多重检验校正后,758个基因转录本中有27个在蛋白质摄入后受到调节(FDR,P值< 0.25)。其中25个上调,2个下调。特别是,参与阿片促黑皮质素原(POMC)加工、免疫功能和IGF信号传导的基因和信号通路发生了显著改变。

结论

PBMC可用于研究长期蛋白质摄入后的基因表达变化,因为蛋白质摄入量增加后许多信号通路受到调节。这些发现的功能意义需要进一步研究。

试验注册

ClinicalTrials.gov,ID号:NCT02218333。该研究于2014年8月18日注册。

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