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