Obesity as a Determinant of Periodontal Therapy Outcomes: Insights on Oxidative and Endoplasmic Reticulum Stress Pathways

Purpose: To assess the impact of non-surgical periodontal treatment (NSPT) on the oxidative and endoplasmic reticulum (ER) stress response of leukocytes, and to examine whether obesity modulates the biological response to periodontal treatment. Methods: Eighty individuals with periodontitis were enrolled and classified according to the presence (n = 42) or absence (n = 38) of obesity. Periodontal parameters –probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), plaque calculus indices and PISA were assessed, along with systemic inflammatory markers (hsCRP, C3c, absolute neutrophil count). Leukocyte oxidative stress (total ROS, cytosolic and mitochondrial superoxide, SOD1, and total antioxidant capacity) and ER stress markers (GRP78, ATF6, p-eIF2α, IRE1α, sXBP1, CHOP) were analysed at baseline and 3 months post-NSPT. Results: NSPT significantly improved all periodontal parameters in both groups, but more so in patients without obesity. Improvement was inversely associated with inflammatory markers, including C3c, systolic blood pressure, and absolute neutrophil count. Obesity was associated with a prooxidative profile with elevated total intracellular ROS, cytosolic superoxide, and SOD1 levels. Following treatment, mitochondrial superoxide, CHOP, and ATF6 decreased, while SOD1, total antioxidant capacity, and GRP78 increased, particularly in the group without obesity. Conclusion: NSPT provides systemic benefits beyond periodontal health, attenuating oxidative and ER stress in leukocytes. Obesity modulates these responses, highlighting redox and ER stress pathways as potential therapeutic targets linking periodontal and metabolic health. Clinical Relevance: This study reinforces the importance of periodontal care providers in the early identification of patients at increased risk of suboptimal periodontal healing. Obesity and systemic inflammatory burden emerge as relevant modifiers of treatment response, indicating that periodontal outcomes are influenced by factors beyond the oral cavity. Incorporating simple clinical information, such as blood pressure and inflammatory status, into routine periodontal assessment would support more individualized treatment planning, optimize follow-up strategies, and improve long-term outcomes in patients with chronic periodontitis.