Sex-Specific Effects of Obesity Severity on Circulating Inflammatory Mediators and Immune Cell Gene Expression

Obesity is characterized by chronic low-grade inflammation and immunometabolic dysfunction. However, the influence of obesity degree on circulating inflammatory mediators and immune-cell-specific molecular pathways remains poorly defined. We aimed to examine the effects of obesity severity on plasma cytokines and adipokines, and on the expression of inflammatory, antioxidant, and mitochondrial genes in peripheral immune cells, with emphasis on gender differences. In this cross-sectional study, 134 adults aged 55-80 years were stratified into overweight, moderate, or severe obesity groups. Plasma cytokine and adipokine levels were quantified with multiplex immunoassays. Gene expression in peripheral blood mononuclear cells and neutrophils was measured by quantitative PCR. Standard hematological parameters were assessed. Two-way analysis of variance and correlation analyses were performed to evaluate associations between obesity severity, gender, circulating biomarkers, and gene expression. Severity of obesity was associated with distinct alterations in circulating inflammatory profiles in a gender-dependent manner. Women exhibited progressive increases in plasma interleukin (IL)-6 with obesity severity, whereas men with severe obesity demonstrated elevated IL-15 and IL-1rα plasma levels. Hematological responses also differed by gender. In contrast, expression of classical inflammatory genes in immune cells was largely unchanged across obesity categories. Women showed higher expression of antioxidant and mitochondrial genes than men, suggesting gender-specific resilience in redox and mitochondrial pathways. Correlations between circulating inflammatory mediators and immune-cell gene expression were generally weak. Obesity severity and gender modulate systemic inflammatory, while immune-cell transcriptional responses are limited, highlighting the importance of gender-specific immunometabolic characterization in obesity research.