Postprandial Responses to a High-Fat Meal: Dependence of Metabolic and Genomic Alterations on the Magnitude of Hypertriglyceridemia in Healthy Young Adults.

Background: Postprandial triglyceridemia (PPT) is proposed as a parameter of risk for cardiovascular disease. However, there is limited information on the mechanisms that relates them. Previous studies on parameter, postprandial triglyceridemia (PPT)-associated changes in different parameters, particularly of inflammation, have provided inconsistent results.

Objectives: This pilot study aimed to investigate whether the magnitude of plasma triglyceride (TG) concentration increases upon consumption of a high-fat meal (HFM) is associated to differential changes in plasma metabolic parameters and endotoxemia and in global gene expression in peripheral blood mononuclear cells (PBMCs).

Methods: Healthy individuals aged 18-40 y, with a body mass index (BMI) (in kg/m²) of >21 and <29.9 consumed a single HFM. Blood was collected before and for 5 h after meal consumption and plasma (0-5 h), and PBMCs (3 h) were isolated. Individuals were separated into 2 groups, those who responded by accumulating plasma TG (mg/dL) in a 5-h period postmeal at concentrations (area under the curve) either <170 [low-postprandial triglyceridemia (LPTG)] or >171 and <700 [high-postprandial triglyceridemia (HPTG)]. Plasma was analyzed for TG, cholesterol, glucose, insulin, and lipopolysaccharide (LPS)-binding protein concentrations. mRNA was isolated from PBMCs for subsequent genomic and qPCR analysis.

Results: Individuals in the HPTG group showed a 4.7-fold increase in both postprandial TG (P < 0.001) and total cholesterol (P = 0.03) compared with those in the LPTG group. Compared with the LPTG group, the HPTG group showed 61% and 180% higher plasma insulin and LPS-binding protein (P = 0.04) concentrations, respectively. Differences in PPT responses also resulted in global transcriptomic differences, including changes in the expression of protein-coding genes as well as noncoding genes (miRNAs and lncRNAs) involved in the immune response, inflammation, and metabolism.

Conclusions: Biochemical and genomic results support the association between a large increase in PPT with a potentially higher risk of developing cardiovascular disease and type 2 diabetes.