ESPE Abstracts (2022) 95 P1-71

1Department of Pediatrics and Pediatric Endocrinology, Faculty of Medical Sciences, Medical University of Silesia, Katowice, Poland; 2Bioinformatics Knowledge Unit, Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion-Israel Institute of Technology, Haifa, Israel; 3Division of Pediatric Endocrinology, Marmara University, School of Medicine, Istanbul, Turkey; 4Department of Human Pathology of Adulthood and Childhood University of MessinaDepartment of Human Pathology of Adulthood and Childhood University of Messina, Messina, Italy; 5Steroid Research and Mass Spectrometry Unit, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany; 6Faculty of Medicine, Technion- Israel Institute of Technology, Haifa, Israel

Context: The response to lifestyle modification (LSM) in children with obesity is variable and difficult to predict.

Aim: A systematic search for molecular markers to predict outcomes of LSM in pediatric obesity management.

Patients/Methods: Out of 240 children with obesity (BMI>97%) recruited to a prospective ‘multi-OMICS’ study granted by ESPE Research Unit, 159 subjects (age 8-17 yrs, median 12.8 yrs; 45% females) finished twelve-months (V12) of LSM obesity management at three centers in Poland, Turkey and Italy. Four of >180 baseline clinical/laboratory (V0) features (sex/age/severity of obesity at V0/delta z-score BMI V12-V0) were used to select 50 representatives for RNA-seq analysis. We searched for circulating mRNA & miRNA capable of predicting the response to LSM defined by a decrease in z-score BMI (Responders/RS). First, the candidate gene approach with previously documented STAT3, CORO1C, SERPINH1, MVP, ITGB5 (upregulated in obesity), PCM1, SIRT1, EEF1G, PTEN and RPS2 (down-regulated in obesity) hub genes was applied. The pairwise ratios of transcripts per million (TPM)s of these genes were tested for statistical significance between RS (n=31) and non-RS (n=19) groups. Secondly, the TPM expression values of 2,129 miRNAs and 33,246 RPL13A-normalized mRNAs were compared between RS and non-RS to get a list of putative significant genes (P< 0.05; the Welch t-test). Enrichr, a web-based tool (, was used for analysing gene sets.

Results: Expression values for 909 mRNA and 24 miRNA genes were significantly different between RS vs non-RS. For example, STAT3/PTEN, CORO1C/PTEN, MVP/PTEN; miRNA-10a, miRNA-122, miRNA-127, miRNA-502, miRNA-210 were significantly higher and SIRT1/PTEN, EEF1G/PTEN, RPS2/PTEN, miRNA-27a were lower comparing RS vs. non-RS (P = 0.009, 0.022, 0.030, 0.048, 0.029, 0.045, 0.035, 0.020, 0.047, 0.04, 0.039, 0.029, respectively). Several pathways, including “Vitamin B6 metabolism" and “Insulin receptor signaling”, were enriched in our differentially expressed mRNA (P<0.001): PNPO, PHOSPHO2, PDXP, PSAT1 were up-regulated in RS vs. non-RS. “Leptin signaling pathway WP2034” were enriched in STAT3 and PTEN (P<0.0001).

Conclusions: The role of the balance between STAT3 and PTEN in LSM was discovered. The importance of previously described miRNA markers (miRNA-122, miRNA-127, miRNA-27a) related to adipogenesis risk, insulin resistance, hepatic fat reduction, PPAR-γ expression were confirmed. A combination of the previously reported V0 Leptin feature together with STAT3/PTEN and miRNA-27a levels showed promising predictive results. Our findings not only showed the predictive molecular markers but also pointed to their role in personalization of therapeutic management.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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