Abstract

Background: Psoriasis is a chronic immune-mediated inflammatory disease associated with systemic comorbidities, particularly obesity and cardiovascular disease. Increasing evidence suggests that obesity is not merely a comorbidity but a key contributor to psoriasis pathogenesis, severity, and therapeutic response through shared inflammatory, metabolic, and immunologic mechanisms. Objective: To review the pathophysiological links between obesity and psoriasis and to evaluate therapeutic strategies targeting obesity, including lifestyle interventions and emerging pharmacologic agents, with emphasis on their implications for disease progression and systemic inflammation. Results: Obesity contributes to psoriasis through chronic low-grade systemic inflammation mediated by adipokines, including leptin, resistin, and adiponectin, as well as immune cell infiltration in adipose tissue. These mechanisms promote Th1 and Th17 activation, endothelial dysfunction, and increased cardiovascular risk. Excess adiposity is associated with increased psoriasis incidence, greater disease severity, and reduced therapeutic response, particularly to biologic agents. Weight reduction through hypocaloric and Mediterranean diets improves psoriasis severity and reduces inflammatory markers. Pharmacologic agents such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the dual GLP-1/GIP agonist tirzepatide demonstrate promising metabolic and anti-inflammatory effects, including reductions in visceral adiposity, inflammatory cytokines, and psoriasis severity in some patients, although responses may vary. Additionally, gut microbiome dysbiosis appears to play a contributory role in systemic inflammation linking obesity and psoriasis, representing a potential therapeutic target. Conclusion: Obesity plays a central role in psoriasis pathophysiology, influencing disease severity, systemic inflammation, cardiovascular risk, and therapeutic outcomes. Integrated management strategies combining weight reduction, metabolic interventions, and targeted immunomodulatory therapies may improve clinical outcomes. Further studies are needed to clarify the long-term effects of obesity-targeted therapies and microbiome modulation in psoriasis management.