This study demonstrates a relationship between fitness level and the amino acid profile. Moreover, the metabolite changes show that a reduced excretion of amino acids in adults is associated with increased fitness levels and an increased fat oxidation rate during exercise. Interestingly, higher levels of branched chain amino acids were associated with lower fitness levels and higher insulin resistance.

This work showed that the within-person variability in postprandial lipemic response is low in most healthy adults. It also showed that variability in this response is associated with a defined set of phenotypic and genotypic characteristics.

Metabolomics is the study of metabolites in biological samples and its application in the field of nutrition and health is increasing exponentially. While much effort has been invested in understanding factors that influence the metabolomic profile there is relatively little known about the effect, fitness level has on the metabolite composition of biofluids. This study aimed to establish the relationship between fitness level, substrate oxidation rates and the metabolomic profile.Two hundred and fourteen healthy adults aged 18-60 years were recruited as part of a metabolic challenge study. The volunteers underwent a sub maximal four stages VO 2 test and had detailed body composition analysis performed. Fasting urine and blood samples were collected. A cohort of sixty-seven subjects (thirty-five male, thirty-two female) were selected based on their estimated VO 2max levels and their biofluid samples were analysed using NMR-and GC-MS-based metabolomics. The subjects were split into fitness groups according to their VO 2max levels (ml/kg/min): females VO 2max < 32; females VO 2max > 43; males VO 2max < 44; males VO 2max > 57.Statistical analysis of the data revealed significant differences in normalised fat and carbohydrate oxidation levels between the fitness groups for females at 15 % and 35 % and males at 35 % of their maximum power output. Females in the high fitness group had significantly higher fat oxidation levels compared to the low fitness group (at 35 %, 0.55°0.20 mg/min/ffm compared to 0.33°0.28 mg/ min/ffm, P = 0.024). Males at 35 % of their power output also had significantly higher fat oxidation levels (0.48°0.23 mg/min/ffm v. 0.31°0.22 mg/min/ffm, P = 0.036). Analysis of the oxygen kinetic data also revealed significant differences between the groups. Both males and females in the high fitness group had significantly decreased recovery time at 55 % and 75 % of their maximum power output (for females: 69.0°15.0 s v. 81.5°17.1 s at 55% maximum power output and 81.0°22.0 s v. 120.5°44.0 at 75 % maximum power output, P = 0.026 and P < 0.001).Metabolomic analysis of the urine samples revealed significantly different profiles in the fitness groups with the differences being more pronounced in the females. A total of twenty amino acids and derivatives were significantly lower in females in the high fitness group. For males, only four amino acids were significantly different. Statistical analysis of the data also revealed correlations in females between 13 amino acid levels in the urine and normalised fat oxidation at 15 % of the maximum power output. In conclusion, this study demonstrates a relationship between fitness level and the metabolomic profile. Moreover, the metabolite changes show that a reduced excretion of amino acids in adults is associated with increased fitness levels and an increased fat oxidation rate during exercise.

Peripheral blood mononuclear cells (PBMC) are an easily accessed tissue type that show differential gene expression following nutritional stimulus in vivo (1) . This study addressed the hypothesis that the PBMC transcriptomic signature and the associated metabolic phenotype would be differentially regulated by lipid v. carbohydrate nutritional challenges (2) . An oral lipid tolerance test (OLTT) and a glucose tolerance test (OGTT) were completed in a 'lean' cohort of ten individuals selected from a representative sample of 200 healthy Irish adults aged 18-60 years (age: 24.6 SD 3.84 years, BMI: 24.5 SD 2.2 kg.m 2 ). Fasting and postprandial peak plasma and 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. The metabolic profile of volunteers was characterised including plasma TAG, NEFA, glucose, insulin and inflammatory profiles were determined.A total of 2292 genes were differentially expressed following OLTT. No single genes were significantly differentially expressed following OGTT. The genes showing greatest changes in expression post-OLTT include CENPK, CLC, OCLN, TMEM176A, FOLR3, ANKRD22, VNN1 and PGA5 (all log Fc >°1.3). Key genes involved in lipid metabolism (LPL, LRP1, PLIN3) and inflammation (IKBKG, NLRP3) were increased following the OLTT, but not OGTT. The KEGG pathway showing greatest enrichment, Fc gamma R-mediated phagocytosis, also contains genes related to inflammation. Most notably, the ERK-activated cPLA2 gene is present, which modulates arachidonic acid (AA) and EPA release from DAG. Given the central role of AA/EPA, this may affect downstream eicosanoid, prostaglandin, leukotriene or resolvin production.The transcriptomic signature will be related to the metabolic phenotype, which included an increase in plasma glucose following the OGTT (P < 0.0001), elevated plasma TAG post-OLTT (P = 0.0354) and lower NEFA concentration following both OGTT (P < 0.0001) and OLTT (P = 0.001). Interestingly the increase in inflammatory gene expression was associated with greater postprandial plasma IL-6 (P = 0.0091) and EGF (P = 0.0053) and a decrease in IFNG (P = 0.104) concentrations post-OLTT, with no such changes post-OGTT.In conclusion, the OLTT induced a pro-inflammatory state in the PBMC transcriptome and plasma protein markers implicated in insulin resistance, the Metabolic Syndrome and T2DM, with no such response following OGTT.