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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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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K. ; Abdulkareem, Ibrahim B. Al ; Al-Dawood, Abdulaziz</creator><creatorcontrib>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</creatorcontrib><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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-018-36007-w</identifier><identifier>PMID: 30573851</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>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</subject><ispartof>Scientific reports, 2018-12, Vol.8 (1), p.17984-8, Article 17984</ispartof><rights>The Author(s) 2018</rights><rights>2018. 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K.</creatorcontrib><creatorcontrib>Abdulkareem, Ibrahim B. Al</creatorcontrib><creatorcontrib>Al-Dawood, Abdulaziz</creatorcontrib><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</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><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.</description><subject>38</subject><subject>45</subject><subject>45/43</subject><subject>631/208</subject><subject>692/308/2056</subject><subject>Adult</subject><subject>Aged</subject><subject>Autophagy</subject><subject>Buffy coat</subject><subject>Caloric Restriction</subject><subject>Critical Care - methods</subject><subject>Critical Care - standards</subject><subject>Critical Illness - therapy</subject><subject>Dietary restrictions</subject><subject>DNA microarrays</subject><subject>Energy Intake - genetics</subject><subject>Enteral feeding</subject><subject>Enteral nutrition</subject><subject>Feeding</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Leukocytes</subject><subject>Leukocytes - metabolism</subject><subject>Male</subject><subject>Malnutrition - blood</subject><subject>Malnutrition - genetics</subject><subject>Middle Aged</subject><subject>multidisciplinary</subject><subject>Nutrition Therapy - methods</subject><subject>Phagocytosis</subject><subject>Regression analysis</subject><subject>Retrospective Studies</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Standard of Care</subject><subject>Transcriptome</subject><subject>Young Adult</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kk1v1DAQhiMEolXpH-CALHHhEvDnJuGAVLYfVKpERbfiaHmTya4rr73YTpftb-yPYra7lMKBHJKJ5_E74_FbFK8Zfc-oqD8kyVRTl5TVpRhRWpWrZ8U-p1KVXHD-_Em8VxymdEPxUbyRrHlZ7AmqKlErtl_cH9u-hwg-W-PIGXggJz-XEVKywRPrySVEu5xDxOz3uc1APrsQOjIG5xJZ2TzfEAuL_C2Qa99B7AE662fE-I5cZXyb2JHT3SIqjqPNtjXOrcm5c-TSZIvl00dyRI4htVgub7SuhmmZ8tCtSehJnsO2zoR8Q8WwsHeATQSfY3AOw0nE_l8VL3rjEhzuvgfF9enJZPylvPh6dj4-uihbWclc9hJA1lMDowZD0QnD8K9npjcj1quqU2wKUnLJTcfrnraCciZYq9qqNpJX4qD4tNVdDtMFdC22j_PRy2gXJq51MFb_nfF2rmfhVo8EZY1sUODdTiCGHwOkrHGCLY7UeAhD0hzvtqmaRilE3_6D3oQhejzeAyWEVHJD8S3VxpBShP6xGUb1xi966xeNftEPftEr3PTm6TEet_x2BwJiCyRM-RnEP7X_I_sLm5TQtA</recordid><startdate>20181220</startdate><enddate>20181220</enddate><creator>Arabi, Yaseen M.</creator><creator>Al-Balwi, Mohammed</creator><creator>Hajeer, Ali H.</creator><creator>Jawdat, Dunia</creator><creator>Sadat, Musharaf</creator><creator>Al-Dorzi, Hasan M.</creator><creator>Tamim, Hani</creator><creator>Afesh, Lara</creator><creator>Almashaqbeh, Walid</creator><creator>Alkadi, Haitham</creator><creator>Alwadaani, Deemah</creator><creator>UdayaRaja, G. 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K.</au><au>Abdulkareem, Ibrahim B. Al</au><au>Al-Dawood, Abdulaziz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2018-12-20</date><risdate>2018</risdate><volume>8</volume><issue>1</issue><spage>17984</spage><epage>8</epage><pages>17984-8</pages><artnum>17984</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30573851</pmid><doi>10.1038/s41598-018-36007-w</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-4145-1890</orcidid><orcidid>https://orcid.org/0000-0003-2910-0390</orcidid><orcidid>https://orcid.org/0000-0002-8071-9837</orcidid><orcidid>https://orcid.org/0000-0002-3772-8949</orcidid><orcidid>https://orcid.org/0000-0001-5735-6241</orcidid><oa>free_for_read</oa></addata></record> |
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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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