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BackgroundObesity is classified as metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO). The current study aimed to screen for relationships and different potential metabolic biomarkers involved between MHO and MUO in adolescents.MethodsThe study included 148 obese adolescents aged between 14 and 16. The study participants were divided into MUO and MHO groups based on the age-specific adolescent metabolic syndrome (MetS) criteria of the International Diabetes Federation. The current study was conducted to investigate the clinical and metabolic differences (AbsoluteIDQ™ p180 kit) between adolescents in the MHO group and those in the MUO group. Multivariate analyses were conducted to investigate the metabolites as independent predictors for the odds ratio and the presence of the MetS in adolescents.ResultsThere were significant differences in the 3 acylcarnitines, 5 amino acids, glutamine/glutamate ratio, 3 biogenic amines, and 2 glycerophospholipids between the obese adolescents in the MUO group and those in the MHO group. Moreover, several metabolites were associated with the prevalence of MUO in adolescents. Additionally, several metabolites were inversely correlated with MHO in adolescents of the MUO group.ConclusionsWe observed that histidine, lysine, PCaaC34:1, and several clinical factors in adolescents of the MUO group were reverse correlated with the results in adolescents of the MHO group. In addition, the triglyceride-glucose index was related to MUO in adolescents, compared with the homeostasis model assessment of insulin resistance. Thus, the biomarkers found in this study have a potential to reflect the clinical outcomes of MUO in adolescents. These biomarkers will lead to a better understanding of MetS in obese adolescents.

Excessive alcohol intake is an important cause of major public health problem in East Asian countries. Growing evidence suggests that genetic factors are associated with alcohol consumption and the risk for alcohol-associated disease, and these factors contribute to the risk of developing chronic diseases, including diabetes. This study aims to investigate the association of type 2 diabetes with genetic polymorphisms within HECTD4 based on alcohol exposure. We performed a genome-wide association study involving the cohorts of the KoGES-HEXA study (n = 50,028) and Ansan and Ansung study (n = 7,980), both of which are prospective cohort studies in Korea. The top three single-nucleotide polymorphisms (SNPs) of the HECTD4 gene, specifically rs77768175, rs2074356 and rs11066280, were found to be significantly associated with alcohol consumption. We found that individuals carrying the variant allele in these SNPs had lower fasting blood glucose, triglyceride, and GGT levels than those with the wild-type allele. Multiple logistic regression showed that statistically significant associations of HECTD4 gene polymorphisms with an increased risk of type 2 diabetes were found in drinkers. Namely, these SNPs were associated with decreased odds of diabetes in the presence of alcohol consumption. As a result of examining the effect of alcohol on the expression of the HECTD4 gene, ethanol increased the expression of HECTD4 in cells, but the level was decreased by NAC treatment. Similar results were obtained from liver samples of mice treated with alcohol. Moreover, a loss of HECTD4 resulted in reduced levels of CYP2E1 and lipogenic gene expression in ethanol-treated cells, while the level of ALDH2 expression increased, indicating a reduction in ethanol-induced hepatotoxicity.

Childhood obesity has increased worldwide, and many clinical and public interventions have attempted to reduce morbidity. We aimed to determine the metabolomic signatures associated with weight control interventions in children with obesity. Forty children from the “Intervention for Children and Adolescent Obesity via Activity and Nutrition (ICAAN)” cohort were selected according to intervention responses. Based on changes in body mass index z-scores, 20 were responders and the remaining non-responders. Their serum metabolites were quantitatively analyzed using capillary electrophoresis time-of-flight mass spectrometry at baseline and after 6 and 18 months of intervention. After 18 months of intervention, the metabolite cluster changes in the responders and non-responders showed a difference on the heatmap, but significant metabolites were not clear. However, regardless of the responses, 13 and 49 metabolites were significant in the group of children with obesity intervention at 6 months and 18 months post-intervention compared to baseline. In addition, the top five metabolic pathways (D-glutamine and D-glutamate metabolism; arginine biosynthesis; alanine, aspartate, and glutamate metabolism; TCA cycle (tricarboxylic acid cycle); valine, leucine, and isoleucine biosynthesis) including several amino acids in the metabolites of obese children after 18 months were significantly changed. Our study showed significantly different metabolomic profiles based on time post obesity-related intervention. Through this study, we can better understand and predict childhood obesity through metabolite analysis and monitoring.