No abstract

The changes of glutamine, methionine, LPCaC18:1, LPCaC18:2, LPCa20:4, and PCaeC36:2 seem to be related to the changes of dieting or exercise habits in lifestyle intervention or to be a consequence of overweight since they normalized in weight loss. Further studies should substantiate our findings.

BCAAs seem to play a pivotal role in the effect of a high-protein diet on β-oxidation and fat storage. We provide new evidence for a possible saturation of the BCAA degradation pathway that may represent the mechanism by which high-protein intake affects the metabolic regulation. Moreover, it appears to inhibit the initial step of the β-oxidation, thus leading to high early weight gain and body fat deposition.

In obese children, hyperinsulinaemia induces adverse metabolic consequences related to the risk of cardiovascular and other disorders. Branched-chain amino acids (BCAA) and acylcarnitines (Carn), involved in amino acid (AA) degradation, were linked to obesity-associated insulin resistance, but these associations yet have not been studied longitudinally in obese children. We studied 80 obese children before and after a one-year lifestyle intervention programme inducing substantial weight loss >0.5 BMI standard deviation scores in 40 children and no weight loss in another 40 children. At baseline and after the 1-year intervention, we assessed insulin resistance (HOMA index), fasting glucose, HbA1c, 2 h glucose in an oral glucose tolerance test, AA, and Carn. BMI adjusted metabolite levels were associated with clinical markers at baseline and after intervention, and changes with the intervention period were evaluated. Only tyrosine was significantly associated with HOMA (p < 0.05) at baseline and end and with change during the intervention (p < 0.05). In contrast, ratios depicting BCAA metabolism were negatively associated with HOMA at baseline (p < 0.05), but not in the longitudinal profiling. Stratified analysis revealed that the children with substantial weight loss drove this association. We conclude that tyrosine alterations in association with insulin resistance precede alteration in BCAA metabolism. This trial is registered with ClinicalTrials.gov Identifier NCT00435734.

Background: Despite the growing interest in the early-origins-of-later-disease hypothesis, little is known about the metabolic underpinnings linking infant weight gain and childhood obesity. Objective: To discover biomarkers reflective of weight change in the first 6 months and overweight/obesity at age 6 years via a targeted metabolomics approach. Design: This analysis comprised 726 infants from a European multicenter randomized trial (Childhood Obesity Programme, CHOP) for whom plasma blood samples at age 6 months and anthropometric data up to the age of 6 years were available. ‘Rapid growth' was defined as a positive difference in weight within the first 6 months of life standardized to WHO growth standards. Weight change was regressed on each of 168 metabolites (acylcarnitines, lysophosphatidylcholines, sphingomyelins, and amino acids). Metabolites significant after Bonferroni's correction were tested as predictors of later overweight/obesity. Results: Among the overall 19 significant metabolites, 4 were associated with rapid growth and 15 were associated with a less-than-ideal weight change. After adjusting for feeding group, only the lysophosphatidylcholine LPCaC14:0 remained significantly associated with rapid weight gain (β = 0.18). Only LPCaC14:0 at age 6 months was predictive of overweight/obesity at age 6 years (OR 1.33; 95% CI 1.04-1.69). Conclusion: LPCa14:0 is strongly related to rapid growth in infancy and childhood overweight/obesity. This suggests that LPCaC14:0 levels may represent a metabolically programmed effect of infant weight gain on the later obesity risk. However, these results require confirmation by independent cohorts.