Location: Immunity and Disease Prevention ResearchTitle: Temporal changes in postprandial blood transcriptomes reveal subject-specific pattern of expression of innate immunity genes after a high-fat meal
|BURNETT, DUSTIN - University Of California, Davis|
Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/12/2019
Publication Date: 6/21/2019
Citation: Lemay, D.G., Huang, S., Huang, L., Alkan, Z., Kirschke, C.P., Burnett, D.J., Wang, Y., Hwang, D.H. 2019. Temporal changes in postprandial blood transcriptomes reveal subject-specific pattern of expression of innate immunity genes after a high-fat meal. Journal of Nutritional Biochemistry. 72:108209. https://doi.org/10.1016/j.jnutbio.2019.06.007.
Interpretive Summary: Modern humans spend most of their time having eaten recently. The purpose of the current project is to understand how the blood, which contains immune cells, responds in the hours after eating a meal that is moderately high in fat. We used a sequencing method to observe the expression of all the genes in blood cells in five participants who were each fed a high fat meal on three separate days. We found that genes involved in inflammation were “turned on” at three and/or six hours after the high-fat meal. We then monitored the expression of specific genes in 20 subjects from the same study. Some participants had a stronger response than others and the timing of the peak response differed between participants. We propose that these genes can be used as biomarkers to determine individual responsiveness to a high-fat meal.
Technical Abstract: Objective: White blood cells are among the first responders to dietary components and their metabolites absorbed from the gut. The objective of the current study was to determine the response of the whole blood transcriptome to a moderately high-fat (36% kcal) meal. Methods A total of 45 fasting and postprandial (3-h and 6-h) whole blood transcriptomes from five subjects in a cross-over intervention trial of the test meal supplemented with placebo, blueberry powder, or docosahexaenoic acid (DHA) were analyzed using RNA sequencing. Select target genes were validated by quantitative RT-PCR in 180 samples from 20 subjects. Results The largest contributor to variance is the subject (13,856 genes differentially expressed), followed by the subject on a specific day (2276 genes), followed by the subject’s postprandial response (651 genes). The universal postprandial response to the test meal (95 genes) was associated with lipid utilization, fatty acid beta-oxidation, and circadian rhythms. Subject-specific postprandial responses to the test meal were enriched for genes involved in the innate immune response, particularly those of pattern recognition receptors and their downstream signaling components. Conclusion Genes involved in innate immune responses are differentially expressed in a subject-specific and time-dependent manner in response to the moderately high-fat meals. These genes can serve as biomarkers to assess individual responsiveness to a high-fat diet in inducing postprandial inflammation. Furthermore, the dynamic temporal change in gene expression in postprandial blood suggests that monitoring these genes at multiple time points is necessary to reveal responders to dietary intervention.