Abstract
BackgroundReported associations between Tumor Necrosis Factor-alpha (TNFA) and the postprandial triacylglycerol (TAG) response have been inconsistent, which could be due to variations in the TNFA gene, meal fat composition or participant’s body weight. Hence, we investigated the association of TNFA polymorphism (−308G → A) with body mass index (BMI) and postprandial lipaemia and also determined the impact of BMI on the association of the polymorphism with postprandial lipaemia.MethodsThe study participants (n = 230) underwent a sequential meal postprandial study. Blood samples were taken at regular intervals after a test breakfast (t = 0, 49 g fat) and lunch (t =330 min, 29 g fat) to measure fasting and postprandial lipids, glucose and insulin. The Metabolic Challenge Study (MECHE) comprising 67 Irish participants who underwent a 54 g fat oral lipid tolerance test was used as a replication cohort. The impact of genotype on postprandial responses was determined using general linear model with adjustment for potential confounders.ResultsThe -308G → A polymorphism showed a significant association with BMI (P = 0.03) and fasting glucose (P = 0.006), where the polymorphism explained 13 % of the variation in the fasting glucose. A 30 % higher incremental area under the curve (IAUC) was observed for the postprandial TAG response in the GG homozygotes than A-allele carriers (P = 0.004) and the genotype explained 19 % of the variation in the IAUC. There was a non-significant trend in the impact of BMI on the association of the genotype with TAG IAUC (P = 0.09). These results were not statistically significant in the MECHE cohort, which could be due to the differences in the sample size, meal composition, baseline lipid profile, allelic diversity and postprandial characterisation of participants across the two cohorts.ConclusionsOur findings suggest that TNFA -308G → A polymorphism may be an important candidate for BMI, fasting glucose and postprandial TAG response. Further studies are required to investigate the mechanistic effects of the polymorphism on glucose and TAG metabolism, and determine whether BMI is an important variable which should be considered in the design of future studies.Trial registration NCT01172951.
Highlights
Reported associations between Tumor Necrosis Factor-alpha (TNFA) and the postprandial triacylglycerol (TAG) response have been inconsistent, which could be due to variations in the TNFA gene, meal fat composition or participant’s body weight
Multiple candidate genes in lipoprotein metabolism pathways have been identified [2,3,4], studies have indicated that genetic variants in tumor necrosis factor-alpha (TNF-α), a cytokine released from macrophages during inflammation, may play an important role in modulating the lipid response to high-fat meal ingestion [5, 6]
TNF-α is expressed in adipocytes and correlates with the degree of adiposity [13]. The effect of this single nucleotide polymorphism (SNP) on lipid and glucose metabolism has been proposed to be dependent on body mass index (BMI) [14] and differences in BMI could be a reason for the discrepancy in the study findings
Summary
Reported associations between Tumor Necrosis Factor-alpha (TNFA) and the postprandial triacylglycerol (TAG) response have been inconsistent, which could be due to variations in the TNFA gene, meal fat composition or participant’s body weight. Multiple candidate genes in lipoprotein metabolism pathways have been identified [2,3,4], studies have indicated that genetic variants in tumor necrosis factor-alpha (TNF-α), a cytokine released from macrophages during inflammation, may play an important role in modulating the lipid response to high-fat meal ingestion [5, 6]. TNF-α is expressed in adipocytes and correlates with the degree of adiposity [13] The effect of this SNP on lipid and glucose metabolism has been proposed to be dependent on body mass index (BMI) [14] and differences in BMI could be a reason for the discrepancy in the study findings. We used an Irish postprandial study, Metabolic Challenge Study (MECHE) [15], as a replication cohort
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