Ahmad S, Hammar U, Kennedy B, et al. - Findings demonstrate association of adiposity with variation of large parts of the circulating metabolome, but causality requires further exploration in well-powered cohorts.

• Three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059) were used to generate metabolomics data to ultimately determine the link between adiposity with circulating metabolites as well as to address causality with Mendelian randomization (MR).

• Body mass index (BMI) was identified to be linked with 77 metabolites, while waist-to-hip ratio adjusted for BMI was related to 11 and 3 metabolites in females and males, respectively.

• Swedish cohorts were analyzed via MR, findings indicated a causal link of increased general adiposity and decreased levels of arachidonic acid, dodecanedioic acid and lysophosphatidylcholine (P-16:0) as well as with raised creatine concentrations.

• A causal link of adiposity on decreased levels of arachidonic acid (p-value 0.03) was supported by the replication effort.