The Interplay Between Obesity and the Renin–Angiotensin System: Molecular Insights and Therapeutic Perspectives

Background and Aim: Obesity is a chronic multifactorial condition that is strongly associated with a wide range of cardiovascular and metabolic complications, including type 2 diabetes mellitus and metabolic syndrome. In addition to its well-established role in blood pressure regulation and electrolyte homeostasis, the renin–angiotensin system (RAS) has emerged as an important regulator of adipocyte biology, inflammatory signaling, oxidative stress, and systemic energy balance. In obesity, excessive activation of the RAS contributes to both metabolic and cardiovascular impairment, particularly through its effects on insulin resistance and chronic low-grade inflammation, supporting a reciprocal relationship between adiposity and RAS activity. This review summarizes current evidence on the obesity–RAS axis and evaluates the therapeutic potential of RAS-targeted strategies in obesity-related disorders. Materials and Methods: A comprehensive review of the literature was undertaken to examine the role of RAS in obesity, with a particular focus on the interaction between the classical and counter-regulatory pathways, as well as the contribution of tissue-specific RAS to inflammation, insulin resistance, and metabolic dysfunction. Results: Available evidence indicates that obesity is associated with increased angiotensin II production in adipose tissue, which promotes chronic inflammation, endothelial dysfunction, insulin resistance, and hypertension. Although central RAS activation may increase thermogenesis and reduce appetite, peripheral RAS activity appears to favor lipogenesis and metabolic deterioration. By contrast, the ACE2/angiotensin-(1–7)/Mas receptor axis exerts beneficial effects by improving vasodilatory capacity, enhancing insulin sensitivity and metabolic homeostasis, and attenuating oxidative stress and inflammatory responses. Consistent with these findings, pharmacological inhibition of the classical RAS, particularly with ACE inhibitors and angiotensin receptor blockers, has shown promising value in reducing obesity-associated metabolic and cardiovascular complications. Conclusion: The relationship between obesity and the RAS is complex and bidirectional. Whereas activation of the classical RAS appears to drive disease progression, the counter-regulatory axis provides an important protective influence. Further studies are needed to refine RAS-based therapeutic strategies and to improve their clinical effectiveness in obesity-related metabolic disorders.