A systematic review of metabolomic studies of childhood obesity: State of the evidence for metabolic determinants and consequences

Abstract

Summary Childhood obesity has become a global epidemic and carries significant long‐term consequences to physical and mental health. Metabolomics, the global profiling of small molecules or metabolites, may reveal the mechanisms of development of childhood obesity and clarify links between obesity and metabolic disease. A systematic review of metabolomic studies of childhood obesity was conducted, following Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, searching across Scopus, Ovid, Web of Science and PubMed databases for articles published from January 1, 2005 to July 8, 2020, retrieving 1271 different records and retaining 41 articles for qualitative synthesis. Study quality was assessed using a modified Newcastle–Ottawa Scale. Thirty‐three studies were conducted on blood, six on urine, three on umbilical cord blood, and one on saliva. Thirty studies were primarily cross‐sectional, five studies were primarily longitudinal, and seven studies examined effects of weight‐loss following a life‐style intervention. A consistent metabolic profile of childhood obesity was observed including amino acids (particularly branched chain and aromatic), carnitines, lipids, and steroids. Although the use of metabolomics in childhood obesity research is still developing, the identified metabolites have provided additional insight into the pathogenesis of many obesity‐related diseases. Further longitudinal research is needed into the role of metabolic profiles and child obesity risk.

Molecular mediators of the association between child obesity and mental health

“…Higher levels of tyrosine (an AAA) and leucine (a BCAA) were associated with obesity, SMFQ, and depression symptoms with consistent effects. Both tyrosine and leucine are widely and consistently associated with childhood obesity ( Handakas et al, 2021 ). A recent study in children showed that high tyrosine levels during life are associated with more internalizing behaviors and negative emotions ( Van Vliet et al, 2019 ).…”

“…Animal studies showed that gut microbiota play a causal role in the development of features of depression ( Kelly et al, 2016 ) and anxiety ( De Palma et al, 2017 ), supporting further evidence that there is a modulation of neurotransmission that is likely a route of communication along the gut-brain axis. Plasma AAAs, which are directly modulated by the gut microbiota ( Handakas et al, 2021 ) could therefore influence later propensity for mental health disorders through metabolic processes of gut and brain interaction. BCAAs, including leucine, play an important role in the activation of the mammalian target of rapamycin (mTor) pathway–a pathway involved in the control of cell growth and proliferation–and has been associated with a short-term decrease in depressive symptoms ( Baranyi et al, 2016 ).…”

“…Although this CpG was identified through the EWAS approach and therefore strongly associated with obesity in this study, it was not among the 483 CpGs identified as putatively associated with body mass in the literature review ( Alfano et al, 2021 ) or the study of ( Wahl et al, 2017 ), suggesting that while it may contribute to poorer mental health among ALSPAC children with obesity, this relationship is unlikely to be generalizable to other populations. To date, few CpGs have been consistently associated with body mass in children ( Vehmeijer et al, 2020 ; Alfano et al, 2021 ), in contrast to adults ( Wahl et al, 2017 ) and indeed metabolites ( Handakas et al, 2021 ). This lack of consistency may be related to the length of time in an obese state, which is shorter for children ( Vehmeijer et al, 2020 ).…”

“…For instance, branched-chain amino acids (BCAAs) may influence brain function by modifying large, neutral amino acid transport at the blood–brain barrier, interfering with neurotransmitter synthesis ( Fernstrom, 2005 ) ( Gruenbaum et al, 2019 ). Recent reviews of the effects of obesity on the epigenome and metabolome in children identified consistent increases in both BCAAs and aromatic amino acids (AAAs) ( Handakas et al, 2021 ) and methylation at multiple CpGs (sites of DNA methylation), albeit with less consistency between studies ( Alfano et al, 2021 ).…”

Metabolomic Fingerprinting for the Detection of Early-Stage Lung Cancer: From the Genome to the Metabolome

“…In addition, as bisphenol A is poorly soluble in water, the presence in blood can result from high levels in drinking water [92]. Finally, it should be pointed out that a number of different factors need to be considered when undertaking metabolomic studies, including diet [110] and comorbidities [111][112][113][114][115][116][117][118][119]. In this regard, obesity [111,112], chronic obstructive pulmonary disease [113][114][115], kidney disease [116], diabetes [117,118], and cardiovascular disease [94] have all been reported to have a major impact on the metabolome that can confound metabolomic studies in cancer, and thus, their influence cannot be underestimated.…”