The prevalence of childhood obesity and obesity-related metabolic disorder such as dyslipidemia has sharply increased in the past few decades. Chronic low-grade inflammation is associated with the development of comorbidities and poor prognosis in obesity. This study aims to evaluate interleukin-10 (IL-10) in childhood obesity with hypertriglyceridemia. We evaluated IL-10 and signal transducer and activator of transcription 3 (STAT3) mRNA expression in adipose tissue (AT) as well as serum IL-10 in 62 children of 3 groups and in high-fat diet (HFD) induced obese rat. Expression of IL-10 and STAT3 protein in AT of diet-induced obese rats were examined over feed period. Adipose IL-10 and STAT3 mRNA expression and serum IL-10 reduced in obese children with hypertriglyceridemia and in HFD obese rats. The protein expression of IL-10 and STAT3 decreased in AT of obese rats compared with the control rats at end time. Expression of IL-10 mRNA was negatively correlated to TG and LDL-C levels, and positively correlated to HDL-C, adiponectin and serum IL-10 levels. IL-10 expression and its downstream JAK-STAT pathway are down-regulated in obese children with hypertriglyceridemia and in HFD obese rats.

Gut microbiota and obesity are deeply interconnected. However, the causality in the relationship between these factors remains unclear. Therefore, this study aimed to elucidate the genetic relationship between gut microbiota and childhood obesity. Genetic summary statistics for the gut microbiota were obtained from the MiBioGen consortium. Genome-wide association studies (GWAS) summary data for childhood obesity were obtained from North American, Australian, and European collaborative genome-wide meta-analyses. Mendelian randomization (MR) analyses were performed using the inverse variance weighting method. 16 children with obesity and 16 without obesity were included for clinical observation, and their weight, body mass index, blood lipid levels, and gut microbiology were assessed. Paired t-test was the primary method of data analysis, and statistical significance was set at P < 0.05. MR identified 16 causal relationships between the gut microbiome and childhood obesity. In the case-control study, we found that five gut microorganisms differed between children with and without obesity, whereas three gut microorganisms changed after weight loss in children with obesity. Our study provides new insights into the genetic mechanisms underlying gut microbiota and childhood obesity. ChiCTR2300072179. Change of intestinal flora and plasma metabolome in obese children and their weight loss intervention: a randomized controlled tria URL OF REGISTRY: https://www.chictr.org.cn/showproj.html. 2023-06-06. 2023-06-07.

Objective: To investigate serum TL1A levels and their correlation with Th17 cells, IL-17, and IL-21 in children with Graves’ disease (GD).Methods: Thirty-seven children (12 males and 25 females) aged 9-14 years with newly diagnosed and untreated GD were enrolled in this study. Serum TL1A, IL-17, and IL-21 levels were measured using enzyme-linked immunosorbent assay (ELISA). The percentage of Th17 cells in peripheral blood was determined by flow cytometry. The correlation between serum TL1A levels and Th17 cells, IL-17, and IL-21 was analyzed using Pearson’s correlation coefficient.Results: Serum TL1A levels and the percentage of Th17 cells were significantly higher in children with GD compared to healthy controls (P<0.05). Serum IL-17 and IL-21 levels were also significantly elevated in GD patients (P<0.05). Serum TL1A levels positively correlated with the percentage of Th17 cells (r=0.625, P<0.05), IL-17 (r=0.573, P<0.05), and IL-21 (r=0.542, P<0.05) in children with GD.Conclusion: Serum TL1A levels are increased in children with GD and positively correlate with Th17 cells, IL-17, and IL-21, suggesting that TL1A may play a role in the pathogenesis of GD by regulating Th17 cell differentiation and the production of IL-17 and IL-21.

Meteorin-like protein (METRNL) has emerged as a novel adipokine involved in metabolic regulation. However, its role in pediatric obesity and its relationship with insulin resistance remain largely unexplored. In this cross-sectional study, we enrolled 55 children with obesity (34 boys, 21 girls) and 49 normal-weight controls (31 boys, 18 girls). Serum levels of METRNL, inflammatory markers (IL-6, TNF-α), and adipokines (leptin, adiponectin) were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to evaluate insulin resistance. Correlations between METRNL and metabolic parameters were analyzed, and multiple regression analysis was performed to identify factors independently associated with insulin resistance. Serum METRNL levels were significantly higher in children with obesity compared to controls (4.62 ± 1.24 vs 2.84 ± 0.76 ng/mL, p < 0.05). METRNL levels showed positive correlations with BMI (r = 0.624, p < 0.05), HOMA-IR (r = 0.594, p < 0.05), inflammatory markers (IL-6: r = 0.528, p < 0.05; TNF-α: r = 0.486, p < 0.05), and leptin (r = 0.546, p < 0.05), while negatively correlating with adiponectin (r = - 0.482, p < 0.05). Multiple regression analysis revealed that METRNL was independently associated with HOMA-IR (standardized β = 0.384, p < 0.05) after adjusting for potential confounders. Serum METRNL levels are elevated in children with obesity and independently associated with insulin resistance. These findings suggest that METRNL might play a significant role in the pathophysiology of pediatric obesity and its metabolic complications. • Meteorin-like protein (METRNL) has emerged as a novel adipokine involved in metabolic regulation. • Serum METRNL concentrations were significantly elevated in children with obesity. • METRNL levels showed positive correlations with BMI, HOMA-IR.

Objective: This study aimed to identify novel proteomic and lipidomic biomarkers of insulin resistance (IR) in young children with obesity and to assess the ability of hub lipids and proteins in the diagnosis of IR. Methods: The discovery cohort consisted of 50 prepubertal children, including 30 children with obesity and 20 lean. The validation cohort included 25 children with obesity and IR (obese‐IR) and 25 children with obesity without IR (obese‐NIR). Fasting plasma was collected from all participants for Olink proteomics and untargeted lipidomics. Pearson correlation analysis was used to identify proteins and lipids associated with IR, and area under the receiver operating characteristic (AUROC) was applied to compare the ability of the identified proteins and lipids with traditional indices in the diagnosis of IR. Results: In the discovery cohort, a total of 15 lipids and 10 proteins had significant correlation with IR. In the validation cohort, protein fatty acid binding protein 4 (FABP4) and gene serpin family E member 1 (PAI) were overexpressed in obese‐IR children compared to obese‐NIR children, while insulin like growth factor binding protein 1 (IGFBP‐1) and paraoxonase 3 (PON3) were lower in the IR group than in the obese‐NIR group; five lipids including sphingosine (d16:0), coenzyme (Q8), ceramides phosphate (d42:2), phosphatidylethanolamine (37:2e), and phosphatidylcholine (18:1e_16:0), showed significant ( p < 0.05) change in obese‐IR children compared to obese‐NIR children. In addition, the AUC‐ROC was 0.89 for IGFBP‐1, 0.81 for PON3, and 0.65 for PAI. The ability of IGFBP‐1, PON3, and PAI to diagnose IR was better than that of adiponectin and leptin. The AUROC of phosphatidylcholine (18:1e_16:0) and coenzyme (Q8) were 0.80 and 0.73, respectively, which was significantly higher than the AUROC of triglycerides(TGs), total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), and low‐density lipoprotein cholesterol (LDL‐C). Conclusion: Proteomic and lipidomic analysis can allow for the identification of potential new candidate biomarkers for IR. The ability of novel biomarkers to diagnose IR was better than traditional indicators. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2300072179