Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo

Obesity is associated with various adverse health outcomes. Body fat (BF) distribution is recognized as an important factor of negative health consequences of obesity. Although metabolomics studies, mainly focused on body mass index (BMI) and waist circumference, have explored the biological mechanisms involved in the development of obesity, these proxy composite measures are not accurate and cannot reflect BF distribution, and thus may hinder accurate assessment of metabolic alterations and differential risk of metabolic disorders among individuals presenting adiposity differently throughout the body. Thus, the exact relations between metabolites and BF remain to be elucidated. Here, we aim to examine the associations of metabolites and metabolic pathways with BF traits which reflect BF distribution. We performed systematic untargeted serum metabolite profiling and dual-energy X-ray absorptiometry (DXA) whole body fat scan for 517 Chinese women. We jointly analyzed DXA-derived four BF phenotypes to detect cross-phenotype metabolite associations and to prioritize important metabolomic factors. Topology-based pathway analysis was used to identify important BF-related biological processes. Finally, we explored the relationships of the identified BF-related candidate metabolites with BF traits in different sex and ethnicity through two independent cohorts. Acetylglycine, the top distinguished finding, was validated for its obesity resistance effect through