Circulating miR-135b as a Biomarker of Obesity-Related Insulin Resistance and Dyslipidemia in Children and Adolescents

  • Pegah Golpour Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, 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 Finetech in Medicine Research Center, 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 Hazrat Aliasghar Children Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Keywords: miR-135b; Obesity; Sirtuin 1; Metabolic syndrome; Insulin resistance

Abstract

Objectives: 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.

Published
2026-06-23
Section
Articles