Differential Gene Expression in Peripheral White Blood Cells with Permissive Underfeeding and Standard Feeding in Critically Ill Patients: A Descriptive Sub-study of the PermiT Randomized Controlled Trial

The effect of short-term caloric restriction on gene expression in critically ill patients has not been studied. In this sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998), we examined gene expression patterns in periphe...

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Veröffentlicht in:Scientific reports 2018-12, Vol.8 (1), p.17984-8, Article 17984
Hauptverfasser: Arabi, Yaseen M., Al-Balwi, Mohammed, Hajeer, Ali H., Jawdat, Dunia, Sadat, Musharaf, Al-Dorzi, Hasan M., Tamim, Hani, Afesh, Lara, Almashaqbeh, Walid, Alkadi, Haitham, Alwadaani, Deemah, UdayaRaja, G. K., Abdulkareem, Ibrahim B. Al, Al-Dawood, Abdulaziz
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container_title Scientific reports
container_volume 8
creator Arabi, Yaseen M.
Al-Balwi, Mohammed
Hajeer, Ali H.
Jawdat, Dunia
Sadat, Musharaf
Al-Dorzi, Hasan M.
Tamim, Hani
Afesh, Lara
Almashaqbeh, Walid
Alkadi, Haitham
Alwadaani, Deemah
UdayaRaja, G. K.
Abdulkareem, Ibrahim B. Al
Al-Dawood, Abdulaziz
description The effect of short-term caloric restriction on gene expression in critically ill patients has not been studied. In this sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998), we examined gene expression patterns in peripheral white blood cells (buffy coat) associated with moderate caloric restriction (permissive underfeeding) in critically ill patients compared to standard feeding. Blood samples collected on study day 1 and 14 were subjected to total RNA extraction and gene expression using microarray analysis. We enrolled 50 patients, 25 in each group. Among 1751 tested genes, 332 genes in 12 pathways were found to be significantly upregulated or downregulated between study day 1 and 14 (global p value for the pathway ≤ 0.05). Using the heatmap, the differential expression of genes from day 1 to 14 in the permissive underfeeding group was compared to the standard feeding group. We further compared gene expression signal intensity in permissive underfeeding compared standard feeding by constructing univariate and multivariate linear regression models on individual patient data. We found differential expression of several genes with permissive underfeeding, most notably those related to metabolism, autophagy and other cellular functions, indicating that moderate differences in caloric intake trigger different cellular pathways.
doi_str_mv 10.1038/s41598-018-36007-w
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We enrolled 50 patients, 25 in each group. Among 1751 tested genes, 332 genes in 12 pathways were found to be significantly upregulated or downregulated between study day 1 and 14 (global p value for the pathway ≤ 0.05). Using the heatmap, the differential expression of genes from day 1 to 14 in the permissive underfeeding group was compared to the standard feeding group. We further compared gene expression signal intensity in permissive underfeeding compared standard feeding by constructing univariate and multivariate linear regression models on individual patient data. 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In this sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998), we examined gene expression patterns in peripheral white blood cells (buffy coat) associated with moderate caloric restriction (permissive underfeeding) in critically ill patients compared to standard feeding. Blood samples collected on study day 1 and 14 were subjected to total RNA extraction and gene expression using microarray analysis. We enrolled 50 patients, 25 in each group. Among 1751 tested genes, 332 genes in 12 pathways were found to be significantly upregulated or downregulated between study day 1 and 14 (global p value for the pathway ≤ 0.05). Using the heatmap, the differential expression of genes from day 1 to 14 in the permissive underfeeding group was compared to the standard feeding group. 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subjects 38
45
45/43
631/208
692/308/2056
Adult
Aged
Autophagy
Buffy coat
Caloric Restriction
Critical Care - methods
Critical Care - standards
Critical Illness - therapy
Dietary restrictions
DNA microarrays
Energy Intake - genetics
Enteral feeding
Enteral nutrition
Feeding
Female
Gene expression
Gene Expression Profiling
Humanities and Social Sciences
Humans
Leukocytes
Leukocytes - metabolism
Male
Malnutrition - blood
Malnutrition - genetics
Middle Aged
multidisciplinary
Nutrition Therapy - methods
Phagocytosis
Regression analysis
Retrospective Studies
Ribonucleic acid
RNA
Science
Science (multidisciplinary)
Standard of Care
Transcriptome
Young Adult
title Differential Gene Expression in Peripheral White Blood Cells with Permissive Underfeeding and Standard Feeding in Critically Ill Patients: A Descriptive Sub-study of the PermiT Randomized Controlled Trial
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