Meal-induced inflammation: postprandial insights from the Personalised REsponses to DIetary Composition Trial (PREDICT) study in 1000 participants

Abstract

Background: Meal-induced metabolic changes trigger an acute inflammatory response, contributing to chronic inflammation and associated diseases.

Objectives: We aimed to characterize variability in postprandial inflammatory responses using traditional (IL-6) and novel [glycoprotein acetylation (GlycA)] biomarkers of inflammation and dissect their biological determinants with a focus on postprandial glycemia and lipemia.

Methods: Postprandial (0-6 h) glucose, triglyceride (TG), IL-6, and GlycA responses were measured at multiple intervals after sequential mixed-nutrient meals (0 h and 4 h) in 1002 healthy adults aged 18-65 y from the PREDICT (Personalised REsponses to DIetary Composition Trial) 1 study, a single-arm dietary intervention study. Measures of habitual diet, blood biochemistry, gut microbiome composition, and visceral fat mass (VFM) were also collected.

Results: The postprandial changes in GlycA and IL-6 concentrations were highly variable between individuals. Participants eliciting an increase in GlycA and IL-6 (60% and 94% of the total participants, respectively) had mean 6-h increases of 11% and 190%, respectively. Peak postprandial TG and glucose concentrations were significantly associated with 6-h GlycA (r = 0.83 and r = 0.24, respectively; both P < 0.001) but not with 6-h IL-6 (both P > 0.26). A random forest model revealed the maximum TG concentration was the strongest postprandial TG predictor of postprandial GlycA and structural equation modeling revealed that VFM and fasting TG were most strongly associated with fasting and postprandial GlycA. Network Mendelian randomization demonstrated a causal link between VFM and fasting GlycA, mediated (28%) by fasting TG. Individuals eliciting enhanced GlycA responses had higher predicted cardiovascular disease risk (using the atherosclerotic disease risk score) than the rest of the cohort.

Conclusions: The variable postprandial increases in GlycA and their associations with TG metabolism highlight the importance of modulating TG in concert with obesity to reduce GlycA and associated low-grade inflammation-related diseases.This trial was registered at clinicaltrials.gov as NCT03479866.

Keywords: glycoprotein acetylation; inflammation; postprandial glycemia; postprandial lipemia; visceral fat mass.

FIGURE 1

Experimental design. Participants arrived fasted for their clinic visit and were given a standardized breakfast (0 h, metabolic challenge meal, 86 g carbohydrate, 53 g fat) and lunch (4 h, 71 g carbohydrate, 22 g fat). Concentrations of glucose, triglycerides, insulin, IL-6, and glycoprotein acetylation were determined from venous blood collected at multiple time points postprandially. Anthropometric, fasting biochemistry, microbiome, and habitual dietary measurements were also made. rRNA, ribosomal RNA.

FIGURE 2

Postprandial changes in IL-6, GlycA, glucose, and TG concentrations (standardized meals consumed at 0 h and 4 h). All n = 1002. (A) Fasting, 4 h, and 6 h postprandial concentrations of IL-6 [ln of IL-6 for all 3 time points (+1)]; (B) fasting, 4 h, and 6 h postprandial GlycA concentrations; (C) fasting, 15, 30, 60, 120, 180, 240, 270, 300, and 360 min glucose concentrations; (D) fasting, 60, 120, 180, 240, 270, 300, and 360 min TG concentrations; (E, F) correlation of features of the postprandial glycemic and lipemic responses with fasting and postprandial (4 and 6 h) inflammatory (IL-6 and GlycA) responses (X = nonsignificant correlation). GlycA, glycoprotein acetylation; TG, triglyceride.

FIGURE 3

Mechanisms underlying postprandial inflammation. (A) Structural equation model to determine the underlying mechanism of postprandial GlycA (6-h) concentrations. Model definitions, with rectangles representing manifest nodes and arrows indicating regression coefficients pointing toward an outcome of regression (standardized β value mentioned on each arrow only for significant associations); n = 1002. (B–D) Scatter plots of the causal effect of (B) visceral fat on fasting GlycA, (C) fasting TG on fasting GlycA, and (D) fasting glucose on fasting GlycA. (E) Network MR. Mediation model for the association between visceral fat and fasting GlycA, with fasting TG as mediator. Path α represents the regression coefficient for the association of visceral fat with fasting TG: “action theory.” Path β represents the regression coefficient for the association of fasting TG with fasting GlycA: “conceptual theory.” The product of regression coefficients α and β (α*β) represents the mediated effect (indirect effect) of fasting TG. Path γ represents the simple total effect of visceral fat on fasting GlycA: “total effect.” GlycA, glycoprotein acetylation; MR, Mendelian randomization; RAPS, robust adjusted profile score; SNP, single nucleotide polymorphism; TG, triglyceride; PCA, principle component analysis.