Original Article
EPIDEMIOLOGY/GENETICS
Study ImportanceWhat is already known? ► In adults, researchers have observed evidence of metabolically healthy obesity and metabolically unhealthy normal weight. ► Little is known regarding the existence of these phenotypes earlier in the life course, and the underlying biological pathways remain unclear.What does this study add?► In 524 adolescents, we found evidence of the existence of metabolically healthy overweight/obesity (OWOB) and metabolically unhealthy normal weight (non-OWOB), in addition to the usual phenotypes of metabolically unhealthy OWOB and metabolically healthy non-OWOB. ► Using untargeted metabolomics profiling of fasting plasma, we identified five metabolite patterns that differ with respect to OWOB status and high vs. low metabolic risk: long-chain fatty acids, branched-chain amino acids, diacylglycerols, steroid hormones, and long-chain acylcarnitines.Objective: The purpose of this article is to characterize metabolomic profiles of four overweight/obesity (OWOB) and metabolic risk (MetRisk) phenotypes among 524 adolescents aged approximately 13 years. Methods: A four-level phenotype variable (non-OWOB and low MetRisk, non-OWOB and high MetRisk, OWOB and low MetRisk, and OWOB and high MetRisk) was created using BMI percentile to define OWOB, and high versus low MetRisk was derived as the fourth versus first to third quartiles of a z score calculated as the average of five externally standardized z scores for waist circumference, homeostatic model assessment of insulin resistance, high-density lipoprotein, triglycerides, and systolic blood pressure. Then associations of nine metabolite patterns derived from principal components analysis with phenotype after accounting for age, sex, race, and pubertal status were evaluated. Results: Five metabolite patterns differed with respect to phenotype: factor 1 consisted of long-chain fatty acids and was lower among non-OWOB and high MetRisk (−0.90 [95% CI: −1.39 to −0.42]) versus non-OWOB and low MetRisk (referent); factors 5 (branched-chain amino acids), 8 (diacylglycerols), and 9 (steroid hormones) were highest among OWOB and high MetRisk; and factor 7 (long-chain acylcarnitines) was higher among non-OWOB and high MetRisk (0.47 [95% CI: 0.04 to 0.91]) and lower among OWOB and low MetRisk (−0.36 [95% CI: −0.68 to −0.04]).Conclusions: Long-chain fatty acids, branched-chain amino acids, acylcarnitines, diacylglycerols, and steroid hormones differed by weight status and metabolic phenotype.