1.
Temporal changes in postprandial blood transcriptomes reveal subject-specific pattern of expression of innate immunity genes after a high-fat meal.
Lemay, DG, Huang, S, Huang, L, Alkan, Z, Kirschke, C, Burnett, DJ, Wang, YE, Hwang, DH
The Journal of nutritional biochemistry. 2019;:108209
Abstract
White blood cells are among the first responders to dietary components and their metabolites absorbed from the gut. The objective of this study was to determine the whole blood transcriptome response to high-fat challenge meals. A total of 45 fasting and postprandial (3-h and 6-h) whole blood transcriptomes from 5 subjects in a crossover intervention trial of a high-fat meal supplemented with placebo, blueberry powder or docosahexaenoic acid (DHA) were analyzed using RNA sequencing. Select target genes were validated by quantitative reverse-transcription polymerase chain reaction in 180 samples from 20 subjects. The largest contributor to variance was 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). After determining the nonsignificance of individual dietary treatments (blueberry, DHA, placebo), treatments were used as replicates to examine postprandial responses to a high-fat meal. The universal postprandial response (95 genes) was associated with lipid utilization, fatty acid beta-oxidation and circadian rhythms. Subject-specific postprandial responses were enriched for genes involved in the innate immune response, particularly those of pattern recognition receptors and their downstream signaling components. Genes involved in innate immune responses are differentially expressed in a subject-specific and time-dependent manner in response to the 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.
2.
Postprandial Endotoxemia Linked With Chylomicrons and Lipopolysaccharides Handling in Obese Versus Lean Men: A Lipid Dose-Effect Trial.
Vors, C, Pineau, G, Drai, J, Meugnier, E, Pesenti, S, Laville, M, Laugerette, F, Malpuech-Brugère, C, Vidal, H, Michalski, MC
The Journal of clinical endocrinology and metabolism. 2015;(9):3427-35
Abstract
CONTEXT Postprandial endotoxemia is a metabolic risk factor, which has been shown to originate from the intestinal absorption of gut lipopolysaccharides (LPS) using nonphysiological high-fat tests. OBJECTIVE This study aimed to determine whether different realistic fat amounts can modulate postprandial dynamics and handling of LPS by varying postprandial lipidemia in humans of different body mass indices. DESIGN, SETTING, AND PARTICIPANTS In a randomized, controlled, cross-over study in nutrition research center, eight normal-weight (NW) and eight obese age-matched men, without diabetes nor dyslipidemia, ingested breakfasts containing 10 vs 40 g fat. Blood samples, leukocytes, and chylomicron-rich fractions were obtained during 8 h. Plasma and chylomicron-endotoxemia, plasma LPS transporters (LBP, sCD14) and IL-6, nuclear factor κB (NF-κB) translocation, and IL-6 gene expression of immune cells were measured. MAIN OUTCOME The postprandial fatty acid handling after ingesting 40 g fat was previously published as primary outcome. The secondary outcomes were inflammatory ones including postprandial endotoxemia, LPS handling, and plasma markers of inflammation after ingesting 10 or 40 g fat. RESULTS Chylomicronemia increased in all subjects according to ingested fat amount (P < .01), but only obese had higher postprandial endotoxemia after 40 g (P < .05). Obese subject chylomicrons were more enriched with LPS compared with NW (PBMI < .01). We observed neither NF-κB translocation, nor variation of IL-6 expression in leukocytes. In both groups, fat amount did not modify postprandial response of plasma IL-6. However, the area under the curve (AUC) of IL-6 in obese was higher than in NW (P < .05) parallel to higher fasting LPS-binding protein (LBP; P < .05). AUC of IL-6 was correlated with LBP (P < .01). CONCLUSION Postprandial endotoxemia is modulated by ingested fat amount in obese men. LPS handling in plasma through chylomicrons and LBP seems critical in driving the acute inflammatory response. The pathophysiological importance of repeated postprandial endotoxemia excursions and their contribution to a vicious cycle of LBP-driven low-grade inflammation deserve further investigation in the nutritional management of cardio-metabolic risk prevention.