Leptin–dopamine interactions: unveiling the common link between type-2 diabetes and neuropsychiatric comorbidities

Clinical evidence highlights the central nervous system as a key target in type-2 diabetes-related complications, yet the mechanisms underlying the increased prevalence of mood disorder issues, mainly depression, in patients with diabetes remain poorly understood. Leptin, an adiposity hormone known for its role in energy homeostasis, has been shown to improve insulin sensitivity and regulate blood glucose levels in diabetic populations. Beyond its metabolic effects, leptin also has the potential to mitigate psychiatric complications such as depression and anxiety. Notably, leptin receptors are predominantly expressed on dopamine (DA) neurons in the brain, hinting that leptin may orchestrate DA activity by serving as its endogenous modulator. This review examines the role of leptin as a potential common link between type-2 diabetes and mood disorders, particularly through its effects on DA function. This article proposes defective leptin signaling as a vital mechanism contributing to psychiatric complications and compromised DA functions in type-2 diabetes, highlighting leptin as a promising therapeutic target for addressing metabolic and psychiatric comorbidities.