Dietary lipids and carbohydrates have key relevance to metabolic health. Postprandial lipid challenges modulate transcriptomic activity in PBMC(1). This study addressed the hypothesis that the metabolic phenotype and associated PBMC transcriptomic signature would be differentially regulated by lipid v. carbohydrate nutritional challenges.
An oral lipid tolerance test (OLTT) and oral glucose tolerance test (OGTT) were completed in a lean, young male cohort of nine individuals selected from a representative sample of 200 healthy Irish adults aged 18–60 years (age: 25, sd 3.84 years, BMI: 23.45, sd 2.3). Plasma was collected at fasting and multiple postprandial time points. Fasting and postprandial peak PBMC samples were taken at 1 and 4 h post OGTT and OLTT, respectively. RNA was hybridised to Affymetrix Human Gene ST 1.0 arrays. Microarray data were normalised using RMA and R/Bioconductor determined differentially expressed genes. A Bayesian algorithm(2) was used to adjust for patient effect. The metabolic profile of volunteers was characterised including plasma TAG, glucose, insulin and c-Peptide. Inflammatory profiles were determined.
There was a marked difference in metabolic marker response between challenges that included an increase in plasma glucose following the OGTT (P<0.0001), elevated plasma TAG post-OLTT (P<0.0001) and lower NEFA concentration following both OGTT (P=0.0031) and OLTT (P=0.0002). Both insulin and c-peptide area under the curve (AUC) were greater following OGTT compared with OLTT. Interestingly the increase in inflammatory gene expression was associated with greater postprandial plasma IL-6 and EGF along with a relative decrease in IFNG concentrations post-OLTT compared with OGTT.
A total of 705 genes were differentially expressed following OLTT. One hundred and forty-eight genes were differentially expressed following OGTT. Genes of particular biological relevance showing differential expression following OLTT related to metabolic health include socs1, irs2 and ifng. Following OGTT, Toll-like receptor signalling pathway gene expression was reduced, including jun, junb, fos, fosb, il8 and mip-1α.
In conclusion, the OLTT-induced plasma protein markers implicated in insulin resistance, the metabolic syndrome and T2DM along with a corresponding pro-inflammatory state in the PBMC transcriptome. In contrast, OGTT showed a reduction in inflammatory gene transcription within PBMC.
This work was conducted as part of a clinical trial (NCT01172951), funded under the Food for Health Research Initiative (NDP 2007–2013; 07FHRIUCD1) by the Department of Agriculture, Fisheries and Food, the Health Research Board and the Department of Health and Children. HMR is supported by Science Foundation Ireland Principal Investigator Programme (06/IM.1/B105).