Metabolomic Signatures of Parental Obesity in Childhood Obesity

Childhood obesity has a multifactorial etiology, involving a complex interplay between endocrine, nutritional, environmental, perinatal, socioeconomic, and psychological determinants. Of these, the family history of obesity stands out as one of the most significant risk factors for the development of obesity in offspring. In this regard, both maternal and paternal obesity have been documented as factors that may trigger programming mechanisms that may result in elevated metabolic risk throughout the lifespan. Furthermore, the intergenerational transmission of parental obesity may occur through lifestyle, as children from families with obesity frequently exhibit a tendency towards unhealthy dietary habits and sedentarism. However, the molecular mechanisms underlying this predisposition remain to be elucidated. In this study, we investigated whether a correlation exists between parental obesity and the presence of persistent metabolic alterations in children with obesity. To this end, a cohort of obese children has been recruited, comprising those with and without parental obesity, in addition to healthy control children. Blood samples were collected for biochemical and inflammatory analysis, while the characterisation of the circulating metabolites was assessed through untargeted metabolomics using a high-throughput LC-MS method. The results indicated that parental obesity was associated with unhealthier metabolic outcomes in children, as evidenced by elevated fasting insulin levels and impaired insulin sensitivity. This was accompanied by alterations in multiple obesity-related metabolic pathways, such as energy homeostasis, amino acid metabolism, oxidative stress, synthesis of steroid hormones and bile acids, membrane lipid composition, and exposome-related metabolites. Notably, some differential metabolites exhibited more pronounced changes in children with parental obesity, especially at the erythroid level, when compared to counterparts without parental obesity. Therefore, we hypothesise that family history of obesity could be an important factor in modulating and exacerbating the characteristic metabolic impairments that typically underly childhood obesity.