Unveiling Molecular Mechanisms Underlying Obesity-Associated Systemic Lupus Erythematosus

Background

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease primarily affecting women of childbearing age, characterised by relapsing inflammation across multiple organ systems. Its aetiology involves genetic and environmental factors that trigger immune dysregulation, leading to the excessive release of autoantibodies.

Objective

This study discusses the pathogenesis, diagnosis, management and emerging therapeutic targets in SLE, with a focus on metabolic reprogramming and the role of obesity.

Methods

Diagnosis is based on clinical and laboratory findings, with the EULAR and ACR criteria being the most advanced. SLE management requires individualised treatment, addressing the severity and organs affected.

Results

SLE presents with symptoms ranging from mild skin rashes to severe conditions like pulmonary hypertension and kidney failure. Advances in care have improved outcomes, with 80%–90% of patients achieving normal life expectancy with proper treatment. Metabolic reprogramming in immune cells is crucial to SLE pathogenesis, as altered glycolysis and fatty acid oxidation contribute to inflammation.

Discussion

Obesity is recognised to aggravate SLE by fostering chronic inflammation, immunological dysregulation and dysbiosis of the gut microbiota. These situations may exacerbate autoimmunity, especially in genetically predisposed individuals. It is suggested that obesity significantly contributes to the pathogenesis of SLE, and additional study should investigate metabolic therapy aimed at obesity and microbiota to re-establish immunological equilibrium and mitigate disease development.

Conclusion

Targeting metabolic pathways may offer new therapeutic options for improved disease management. Particular abnormalities in gut microbiota, characterised by reduced diversity and an increase in pro-inflammatory species, influence obesity-related immunological dysregulation in systemic lupus erythematosus and may present new therapeutic targets.