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258plasma HDL cholesterol and decreases LDL choles-terol, free fatty acids, and triglycerides18). Although cobalt may reduce childhood BMI by influencing lipid metabolism, we did not determine the level of leptin in the participants of the present study. Another possible underlying mechanism might be iron metabolism, as iron plays an important role during rapid growth periods, such as adolescence. A recent study reported lower iron concentrations in children and adolescents who are overweight and a 50 % incidence of iron-deficiency anemia in individuals with a BMI above the 97th percentile44). Cobalt may influence iron metabolism, conse-quently increasing obesity risk by increasing the hemoglobin, hematocrit, and red blood cell counts in men45). Thus, cobalt may influence BMI by changing the metabolism of glucose, lipids, and iron differently in men and women. In the present study, with a relatively large sample size, we considered several potentially confounding factors. However, the limitations of this study need to be addressed. First, the cross-sec-tional design of the present study may not draw conclusions regarding the causal relationship between UCo and childhood BMI. The generaliz-ability of the results might be limited owing to the study design. Second, child anthropometric charac-teristics (i.e., weight and height) develop over several months to years; thus, a single UCo measurement may not reflect cumulative concen-trations or exposure levels at an earlier life. Third, urinary excretion of cobalt is multiphasic, with a rapid increase in hours and a peak of elimination at 24 h following exposure46). In other words, the current study obtained the level of cobalt exposure via measurement of one spot-urine sample. It would be better to collect a 24 h urine sample for cobalt measurements. Finally, some considerable confounding factors associated with weight and BMI, such as the participants’ diet and physical activities, were not adjusted for in the current study because information on these was limited in the TTC dataset.In summary, among the 18 measured trace elements in the present study, only cobalt showed a significant inverse relationship with BMI in Japa-nese boys. Thus, cobalt may have sufficient potency to decrease the risk of obesity in children. Future epidemiological and experimental studies may need to clarify the magnitude of the effect and under-lying mechanism(s).This work is a part of the Tokyo Teen Cohort Study, and we would like to thank all researchers, investigators, and participants for their substantial support in sample collection and management. We would like to express our deep thanks to Dr. Mohsen Vigeh for supporting the manuscript preparation. We are grateful to Ms. Shizuka Iwasaki for assistance in the preparation of analytical solu-tions. We would like to thank Editage (www.editage.com) for English language editing.This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas (23118002; Adolescent Mind & Self-Regulation) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number JP19H01081).Conception and design, JT and TM. Formal anal-ysis and drafting of the article, JT. Critical revision for important intellectual content, KY, SY, SA, AN, MHH, and KK. Measurement of trace elements’ concentration, TM. All authors read and approved the final manuscript.The authors declare that they have no conflicts of interest.The present study was conducted after approval was received from the ethics committees of the Tokyo Metropolitan Institute of Medical Science (approval no. 14-08) and Juntendo University (approval no. 2016092).Written informed consent was obtained from each participant and the participant’s primary parent before participation, as part of the Tokyo Teen Cohort study.AcknowledgementsFundingAuthor contributionsConflicts of interest statementEthics approvalConsent to participate