Follistatin-Like 1 and Family with Sequence Similarity to 19 Member A5 Levels Are Decreased in Obese Children and Associated with Glucose Metabolism.

INTRODUCTION: Childhood obesity is a significant and growing problem worldwide. Recent evidence suggests Follistatin-like 1 (FSTL1) and family with sequence similarity to 19 member A5 (FAM19A5) to be novel adipokines. However, very few studies have examined the plasma levels of FSTL1 and FAM19A5 in children. Therefore, this cross-sectional study evaluated the association between serum FSTL1 and FAM19A5 levels and obesity in children and investigated the relationship between FSTL1 and FAM19A5 and glucose metabolism or endothelial injury. METHODS: Fifty-five obese children and 48 healthy controls were recruited. Plasma FSTL1 and FAM19A5 levels were detected using ELISA. In addition, the association between the clinical data and anthropometric parameters was analyzed. RESULTS: Serum FAM19A5 levels were significantly decreased in the obese children, at 189.39 ± 19.10 pg/mL, compared with those without obesity, at 211.08 ± 38.09 pg/mL. Serum concentrations of FSTL1 were also significantly lower in the obese children, at 0.64 (0.37-0.64) ng/mL, compared with those without obesity, at 1.35 (1.05-2.12) ng/mL. In addition, FAM19A5 (OR = 0.943; p = 0.003) was a predictor of insulin resistance in obese children compared with healthy controls. Lastly, serum FAM19A5 and FSTL1 played mediating roles in insulin resistance in children. CONCLUSION: The serum levels of FAM19A5 and FSTL1 were decreased in obese children; therefore, FAM19A5 and FSTL1 likely play important roles in glucose metabolism in obese children.

Copeptin and Nesfatin-1 Are Interrelated Biomarkers with Roles in the Pathogenesis of Insulin Resistance in Chinese Children with Obesity.

BACKGROUND: Copeptin and nesfatin-1 have recently been identified as novel peptides that play a role in the pathogenesis of obesity-related insulin resistance in adults. However, the relationship between them has not yet been elucidated, and their circulating levels in children with obesity have not been adequately studied. Therefore, the current study aimed to investigate whether their levels are altered in Chinese children with obesity, as well as to determine the correlation of these 2 peptides with each other, with insulin resistance, and with other biochemical parameters. METHODS: A total of 156 children were enrolled in this study, including 101 children with obesity and 55 lean controls. Anthropometric parameters and clinical data of all subjects were collected, and circulating tumor necrosis factor-α, adiponectin, leptin, copeptin, and nesfatin-1 levels were measured using ELISA. RESULTS: Serum copeptin and nesfatin-1 levels were significantly elevated in children with obesity and children with insulin resistance compared to control subjects. In addition, nesfatin-1 and copeptin levels were found to be significantly positively correlated with one another by Pearson's correlation and partial correlation. In multiple regression analysis using nesfatin-1 or copeptin as the dependent parameter, a significant correlation was observed between nesfatin-1 and copeptin, and associations between each of them with homeostasis model assessment of insulin resistance (HOMA-IR) were detected. CONCLUSION: These novel findings shed light on the possible interplay role of these 2 molecules in obesity-related insulin resistance.

Irisin as a mediator between obesity and vascular inflammation in Chinese children and adolescents.

BACKGROUND AND AIM: This study aims to characterize the role of Irisin in obesity and early onset metabolic and vascular sequelae in Chinese children. Furthermore, we aim to examine whether Irisin mediate endothelial cells dysfunction and vascular inflammation which eventually leads to obesity. METHODS AND RESULTS: We quantified plasma Irisin levels using enzyme-linked immunosorbent assay (ELISA) among 85 lean and 120 obese children, and assessed the association of Irisin levels with anthropometric, metabolic, cardiovascular and inflammatory parameters of obese children comparing with lean children. We further characterized the markers for endothelial cells and inflammation between obese and lean children to assess potential correlations. In addition, a potential direct effect of Irisin on the expression of endothelial adhesion molecules was assessed in human coronary artery endothelial cells. Irisin levels from obese children was significantly lower than lean children, and this reduced Irisin levels is correlated with certain physical parameters of studied children. Moreover, we identified significant inverse associations between inflammation markers of endothelial activation with Irisin levels in obese children. Multiple regression analyses confirm Irisin serves as a strong predictor of SDS-SBP, Ang-2, ICAM-1, E-selectin and hsCRP levels, independent of SDS-BMI. Lifestyle intervention results in a significant improvement of these cardiovascular and inflammatory parameters, and these were accompanied by a significant improvement of Irisin levels and weight loss. Finally, in the mediation effect model, our data showed that Irisin changes act as partial mediators of the relationship between SDS-BMI changes and changes in inflammatory and endothelial parameters for ICAM-1, E-selectin and hsCRP after controlling for covariates. Likewise, on the cellular level, Irisin inhibition hsCPR, ICAM-1 and E-selectin expression in endothelial cells, whereas Ang-2, VCAM-1 and eNOS expression were unaffected. CONCLUSIONS: Our study showed that Irisin levels change may indicate the early stages of cardiovascular disease in obese children.