BackgroundIn recent years an individual’s ability to respond to an acute dietary challenge has emerged as a measure of their biological flexibility. Analysis of such responses has been proposed to be an indicator of health status. However, for this to be fully realised further work on differential responses to nutritional challenge is needed. This study examined whether metabolic phenotyping could identify differential responders to an oral glucose tolerance test (OGTT) and examined the phenotypic basis of the response.Methods and ResultsA total of 214 individuals were recruited and underwent challenge tests in the form of an OGTT and an oral lipid tolerance test (OLTT). Detailed biochemical parameters, body composition and fitness tests were recorded. Mixed model clustering was employed to define 4 metabotypes consisting of 4 different responses to an OGTT. Cluster 1 was of particular interest, with this metabotype having the highest BMI, triacylglycerol, hsCRP, c-peptide, insulin and HOMA- IR score and lowest VO2max. Cluster 1 had a reduced beta cell function and a differential response to insulin and c-peptide during an OGTT. Additionally, cluster 1 displayed a differential response to the OLTT.ConclusionsThis work demonstrated that there were four distinct metabolic responses to the OGTT. Classification of subjects based on their response curves revealed an “at risk” metabolic phenotype.

The role of metabolomics in the field of nutrition is continuing to grow and it has the potential to assist in the understanding of metabolic regulation and explain how minor perturbations can have a multitude of biochemical endpoints. It is this development, which creates the potential to provide the knowledge necessary to facilitate a more targeted approach to nutrition. In recent years, there has been interest in applying metabolomics to examine alterations in the metabolic profile according to weight gain/obesity. Emerging from these studies is the strong evidence that alterations in the amino acid (AA) profiles are associated with obesity. Several other studies have also shown a relationship between branched-chain amino acids (BCAA), obesity and insulin resistance. The present review focuses on the proposed link between AA and in particular BCAA, obesity and insulin resistance. In conclusion, a wealth of information is accumulating to support the role of AA, and in particular of the BCAA, in obesity. Metabolomics: Amino acids: BMI: Branched-chain amino acidsObesity is now considered as a major global health problem, and the WHO has demonstrated that obesity levels have reached epidemic proportions worldwide with approximately 2 . 3 billion adults predicted to be overweight or obese by the year 2015(1) . It is well recognised that obesity plays a central role in insulin resistance, the metabolic syndrome and type-2 diabetes mellitus. Despite many years of research the exact mechanisms underlying the role of obesity in the development of these disorders and diseases are still not fully elucidated. However, in recent years, the application of 'omic' technologies to studies comparing lean and obese subjects has enhanced our understanding of this research area. This review will focus on the literature, which has utilised metabolomic techniques to investigate the altered metabolic profile in obesity and the subsequent effect on insulin resistance. MetabolomicsMetabolomics is the comprehensive study of metabolites in biofluids, tissues or cellular extracts. The metabolic profile of a sample may be assessed using a variety of techniques including Proton NMR spectroscopy, LC-MS and GC-MS. The role of metabolomics in the field of nutrition is continuing to grow and its utility in a number of studies has been demonstrated (2,3) . Earlier applications of metabolomics in this field compared metabolic profiles of lean and obese subjects (Table 1). Pietiläinen et al.(4) investigated whether acquired obesity was associated with changes in global serum lipid profiles independent of genetic factors in young adult monozygotic twins. In this study, fourteen healthy monozygotic pairs discordant for obesity (10-25 kg weight Abbreviations: AA, amino acid; BCAA, branched-chain amino acid; GBP, gastric bypass surgery; HF, high fat.

The objectives of the present study were to (1) examine the effects of the phenotypic factors age, gender and BMI on the lipidomic profile and (2) investigate the relationship between the lipidome, inflammatory markers and insulin resistance. Specific ceramide, phosphatidylcholine and phosphatidylethanolamine lipids were increased in females relative to males and specific lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidylcholine and phosphatidylethanolamine lipids decreased as BMI increased. However, age had a minimal effect on the lipid profile with significant differences found in only two lipid species. Network analysis revealed strong negative correlations between the inflammatory markers CRP, TNF-α, resistin and MCP-1 and lipids in the LPC, PC and PE classes, whereas IL-8 formed positive correlations with lipids from the CER and SM classes. Further analysis revealed that LPC a C18:1 and PE ae C40:6 were highly associated with insulin resistance as indicated by HOMA-IR score. The present study identified lipids that are affected by BMI and gender and identified a series of lipids which had significant relationships with inflammatory markers. LPC a C18:1 and PE ae C40:6 were found to be highly associated with insulin resistance pointing to the possibility that the alterations in these specific lipids may play a role in the development of insulin resistance.

The PBMC transcriptome may therefore provide a unique insight into the inflammatory component of metabolic health, as opposed to directly reflecting the metabolic component of the adipose tissue transcriptome.

No abstract

BackgroundThe lipid composition of plasma is known to vary due to both phenotypic factors such as age, gender and BMI as well as with various diseases including cancer and neurological disorders. However, there is little investigation into the variation in the lipidome due to exercise and/ or metabolic challenges. The objectives of this present study were (i) To identify the glycerophospholipid, sphingolipids and ceramide changes in response to an oral lipid tolerance test (OLTT) in healthy adults and (ii) To identify the effect of aerobic fitness level on lipidomic profiles.Methods214 healthy adults aged 18–60 years were recruited as part of a metabolic challenge study. A sub-group of 40 volunteers were selected for lipidomic analysis based on their aerobic fitness level. Ceramides, glycerophospholipids and sphingomyelins were quantified in baseline fasting plasma samples as well as at 60, 120, 180, 240 and 300 min following a lipid challenge using high-throughput flow injection ESI-MS/MS.ResultsMixed model repeated measures analysis identified lipids which were significantly changing over the time course of the lipid challenge. Included in these lipids were lysophosphoethanolamines (LPE), phosphoethanolamines (PE), phosphoglycerides (PG) and ceramides (Cer). Five lipids (LPE a C18:2, LPE a C18:1, PE aa C36:2, PE aa C36:3 and N-C16:1-Cer) had a fold change > 1.5 at 120 min following the challenge and these lipids remained elevated. Furthermore, three of these lipids (LPE a C18:2, PE aa C36:2 and PE aa C36:3) were predictive of fasting and peak plasma TAG concentrations following the OLTT. Further analysis revealed that fitness level has a significant impact on the response to the OLTT: in particular significant differences between fitness groups were observed for phosphatidylcholines (PC), sphingomyelins (SM) and ceramides.ConclusionThis study identified specific lipids which were modulated by an acute lipid challenge. Furthermore, it identified a series of lipids which were modulated by fitness level. Future lipidomic studies should take into account environmental factors such as diet and fitness level during biomarker discovery work.Trial registrationData, clinicaltrials.gov, NCT01172951Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-015-0062-x) contains supplementary material, which is available to authorized users.

Our results indicate that BMI is strongly linked to the transcriptomic and metabolic response to acute challenges. The emerging biological processes are mainly inflammation-related pathways, highlighting an interconnection between obesity, inflammation/adhesion, and response to nutritional challenge. The comparison between lipid and glucose challenges shows how these trigger a substantially different molecular response.

The OLTT induced some gender-specific correlations of gene coexpression network modules. In females, biological processes relating to energy metabolism and inflammation pathways were evident. This suggests a gender specific link between inflammation and energy metabolism in response to lipids. In contrast, G-protein coupled receptor protein signaling pathway was common to both genders.