Metabolomic profiles and childhood obesity

Abstract

Objective To identify metabolite patterns associated with childhood obesity, to examine relations of these patterns with measures of adiposity and cardiometabolic risk, and to evaluate associations with maternal peripartum characteristics. Design and Methods We employed untargeted metabolomic profiling to quantify metabolites in plasma of 262 children (6–10 years). We used principal components analysis to consolidate 345 metabolites into 18 factors and identified two that differed between obese (BMI ≥95%ile; n=84) and lean children (BMI<85%ile; n=150). We then investigated relations of these factors with adiposity (fat mass, BMI, skinfold thicknesses) and cardiometabolic biomarkers (HOMA-IR, triglycerides, leptin, adiponectin, hsCRP, IL-6) using multivariable linear regression. Finally, we examined associations of maternal pre-pregnancy obesity, gestational weight gain, and gestational glucose tolerance with the offspring metabolite patterns. Results A branched-chain amino acid (BCAA)-related pattern and an androgen hormone pattern were higher in obese vs. lean children. Both patterns were associated with adiposity and worse cardiometabolic profiles. For example, each increment in the BCAA and androgen pattern scores corresponded with 6% (95% CI: 1%, 13%) higher HOMA-IR. Children of obese mothers had 0.61 (0.13, 1.08) higher BCAA score than their counterparts. Conclusions BCAA and androgen metabolites were associated with adiposity and cardiometabolic risk during mid-childhood. Maternal obesity may contribute to altered offspring BCAA metabolism.

Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism

“…Although MSC were selected based on maternal prepregnancy BMI, there was great heterogeneic overlap in adiposity and maternal FFA concentrations between the OB and NW groups. We therefore tested relationships using both groups combined (when the phenotypic variable was continuous) and also within OB offspring specifically, as this is the group with the highest risk for metabolic derangements as children (16).…”

“…Similarly, in adipocytes from OB adults, there is decreased fatty acid oxidation, increased lipogenesis, and spared amino acid catabolism (13,20,21). Biomarkers for these processes can be observed in plasma of OB school-aged children (16,22,23), suggesting early changes in mitochondria metabolism in established obesity.…”

“…Increased circulating plasma short-and long-chain acylcarnitines (LCAC) (12)(13)(14) and multiple amino acids including branched chain, aromatic (e.g., phenylalanine and tyrosine), 1-carbon (e.g., methionine, cysteine, and glycine), and glutaminolytic (e.g., aspartate, alanine, and glutamine) are associated with insulin resistance and established obesity. Amino acid changes are thought to be largely due to anaplerosis, or the use of amino acid oxidative catabolism to replenish tricarboxylic acid cycle (TCA cycle) intermediates in the setting of incomplete β-oxidation (12)(13)(14)(15)(16). In myocytes from OB adults, there is reduced fatty acid oxidation, leading to elevations in long-and medium-chain acylcarnitines and anaplerosis, and decreased oxidative phosphorylation, indicating abnormalities in key energy pathways (13,(17)(18)(19).…”

Associations of cord blood metabolites with perinatal characteristics, newborn anthropometry, and cord blood hormones in project viva

“…The study sample for this analysis comprised 126 of 262 mother-child pairs from a published study on mid-childhood metabolite patterns, obesity, and metabolic risk (10). The only inclusion criteria for the present study was available cord blood for the metabolomics assays (≥50 uL; n = 126).…”

“…Metabolomics analyses in children have found that higher circulating branched chain amino acids (BCAAs) are associated with obesity status (10, 11), as well as subclinical risk factors for metabolic disease like insulin resistance (10, 12). Studies in adults have shown that elevations in serum branched chain amino acids (BCAAs) are detectable several years prior to development of insulin resistance and incident type 2 diabetes (13, 14), even among individuals of similar weight status (13).…”