RNA-based approaches in the diagnosis and treatment of obesity

Obesity is a global, complex, and multifactorial disease, and a major risk factor for diabetes, cardiovascular disease, fatty liver disease, and cancer. Despite its high prevalence, effective diagnostic and therapeutic strategies remain limited. Conventional anthropometric measurements, such as body mass index (BMI) and waist circumference, offer limited accuracy in assessing the impact of excess adiposity and related comorbidities on individual patients. Current anti-obesity pharmacotherapies also show inconsistent efficacy, are often associated with systemic side effects, and poor adherence to necessary lifestyle modifications, which limit their long-term success. Emerging evidence underscores the critical role of non-coding RNAs, including microRNAs, long non-coding RNAs, circular RNAs, and tRNA-derived small RNAs in key metabolic processes such as adipogenesis, insulin signalling, and appetite control. Notably, the profiles of many circulating miRNAs have been reported to differ between patients with obesity compared to healthy lean individuals, suggesting their potential as minimally invasive diagnostic biomarkers. In this mini-review, we discuss the clinical promise of RNA-based approaches for disease risk assessment and as therapeutic targets in obesity. In addition, we discuss key challenges, including biomarker validation and effective RNA delivery systems to the target organs. Multi-omics approaches may help overcome many of these limitations and enable the development of targeted and personalized RNA-based anti-obesity therapies.