The relationship between BMI and metabolomic profiles: a focus on amino acids

Abstract

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.

Metabolomics identifies changes in fatty acid and amino acid profiles in serum of overweight older adults following a weight loss intervention

“…Higher levels of circulating BCAAs have been reported in obese individuals compared to lean individuals [35,39], with a number of studies reporting a reduction in BCAAs levels after weight loss [26,28]. BCAAs predicted improvements in insulin resistance in patients participating in a weight loss intervention [31,49], and a positive association between BCAAs and insulin resistance has been also reported [34,49].…”

Effects of pre-analytical processes on blood samples used in metabolomics studies

“…in the study design and sample-collection procedureFactorRecommendationsMain metabolites and references (selected examples)Sex a Match the distribution of sexLipids [45, 46], orthophosphate, α-tocopherol, creatinine, DHEA-S [47], cholesterol [44]AgeMatch the distribution of ageAmino acids [48], isocitrate, succinate, malate, lactate, etc. [47]Body mass index (BMI)Refer to BMI before the enrollment of participants, and match for BMIBCAA [49–51], lipids, steroids [52]Fasting and feeding12 h fasting (usually overnight)Essential amino acids and acylcarnitines [53], triglycerides and homocysteine [54]Circadian rhythmKeep normal biorhythm; collect samples at the same time point (usually in the morning); take circadian rhythm into account if metabolite concentrations follow a rhythmLipids [55], BCAA, lactate [56], bilirubin, cortisol [56, 57]Exercise; stressAvoid unaccustomed physical activity; avoid stress before drawing bloodLactate, free fatty acids, glucose, amino acids and acylcarnitines [53, 58], uric acid [44], creatinine and many othersDrugs and/or nutritional supplements (e.g. vitamins, amino acids)At least 12 h abstention, preferably 24 h or longer–

a Sex-specific differences in metabolite concentrations should always be assumed until proved otherwise

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Acne: Risk Indicator for Increased Body Mass Index and Insulin Resistance

“…Not by chance, milk provides highest amounts of leucine in comparison to all other animal proteins to optimise mTORC1 activation for postnatal growth. Several recent metabolomics studies underline the relationship between high plasma BCAA profiles, increased BMI and insulin resistance recently reviewed by Morris et al (18). Thus, acne appears to develop in a metabolic environment with increased mTORC1 signalling and has been proposed to represent a visible mTORC1-driven disease of civilisation (19).…”

“…First evidence supporting a correlation between milk consumption and BMI has been provided by the Growing Up Today Study (10 and pivotal activators of the amino acid-sensitive enzyme mTORC1, have been associated with obesity and future insulin resistance in children and adolescents in the United States (22). There is accumulating evidence that high plasma levels of BCAAs are associated with insulin resistance (18). In fact, Hoppe et al (23) have demonstrated that high intake of milk protein (53 g/ day), but not meat (53 g/day) increased basal insulin serum levels and induced insulin resistance in 8-yearold Danish boys.…”