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.
Highlights
Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia. 4Cord Blood Bank, King Abdullah International Medical
Evidence from recent randomized controlled trials and systematic reviews showed that short-term caloric restriction in the acute phase of critically ill patients was not associated with significant differences in mortality[1,2,3,4,5,6], and might be associated with reduced bloodstream infections, acute kidney injury and mechanical ventilation duration[4,6]
The objective of this study is to examine gene expression patterns in peripheral white blood cells associated with moderate caloric restriction in critically ill patients compared to standard feeding
Summary
Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia. 4Cord Blood Bank, King Abdullah International Medical. Evidence from recent randomized controlled trials and systematic reviews showed that short-term caloric restriction in the acute phase of critically ill patients was not associated with significant differences in mortality[1,2,3,4,5,6], and might be associated with reduced bloodstream infections, acute kidney injury and mechanical ventilation duration[4,6]. Two randomized controlled trials found that delaying parenteral nutrition for 1 week was associated with improved outcomes in adult and pediatric critically ill patients[7,8]. The effect of short-term caloric restriction on gene expression in critically ill patients has not been studied. The objective of this study is to examine gene expression patterns in peripheral white blood cells associated with moderate caloric restriction (permissive underfeeding) in critically ill patients compared to standard feeding
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