Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 3 4 2025 12 21 226 234 Pegah Golpour Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Saeedeh Moradgholi Department of Biochemistry, Faculty of Biological Sciences, North-Tehran Branch, Islamic Azad University, Tehran, Iran Zahra Arab Sadeghabadi Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran Mona Nourbakhsh Hazrat Aliasghar Children Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mitra Nourbakhsh Department of Clinical Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Zeynab Yousefi Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Maryam Razzaghy-Azar Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. 2025 11 21 2026 01 04 Objective: Childhood obesity is a global health concern associated with long-term metabolic complications. MicroRNA-135b (miR-135b) has been implicated in regulating adipogenesis, glucose metabolism, and insulin signaling, partly by directly targeting SIRT1, a key metabolic regulator that plays a crucial role in energy homeostasis and inflammation. However, the role of miR-135b in pediatric obesity remains unclear. This study aimed to investigate circulating miR-135b level and its relationship with SIRT1 expression, lipid profile, and glycemic parameters in children and adolescents with obesity. Methods: A total of 67 participants (36 obese and 31 normal-weight controls) aged 8–16 years were enrolled. Anthropometric measurements and biochemical analyses were performed. miR-135b and SIRT1 expression levels were measured using quantitative real-time PCR. Insulin resistance was assessed using HOMA-IR, and metabolic syndrome was diagnosed based on International Diabetes Federation criteria. Results: miR-135b expression was significantly elevated in the obesity group compared to controls and was highest among participants with insulin resistance and metabolic syndrome. Elevated miR-135b correlated positively with BMI z-score, insulin levels, HOMA-IR, total cholesterol, triglycerides, and LDL-C, while showing no significant correlation with HDL-C. In contrast, SIRT1 expression was significantly decreased in obese individuals (p = 0.0026) and inversely correlated with miR-135b levels. Conclusion: Elevated miR-135b and reduced SIRT1 expression are associated with obesity-related metabolic disturbances in children and adolescents. These findings suggest that the miR-135b/SIRT1 axis may play a pivotal role in the development of insulin resistance and dyslipidemia, highlighting miR-135b as a potential biomarker and therapeutic target for early intervention in pediatric obesity. https://abi.tums.ac.ir/index.php/abi/article/view/167 https://abi.tums.ac.ir/index.php/abi/article/download/167/124