Sex dimorphism in inflammatory response to obesity in childhood

Childhood overweight and obesity are a global concern, with prevalence rising dramatically over the last decades. The condition is caused by an increase in energy intake and reduction of physical activity, leading to excessive fat accumulation, followed by systemic chronic inflammation and altered function of immune cell responses. This study aimed at providing new insights regarding sex-specificity on the inflammatory response to obesity in the young patient.

Forty-three Brazilian obese adolescents (Female = 22 and Male=21, BMI (body mass index) Z-score average = 2.78 ± 0.51) and forty-nine eutrophic adolescents (Female = 24 and Male = 25, BMI Z-score average = -0.35 ± 0.88) were enrolled in the study. Anthropometrical analyses and blood cell counts were carried out. Using Luminex®xMAP™ technology, circulating serum cytokines, chemokines, and inflammatory biomarkers were analyzed. Two-way ANOVA test, Tukey's test, and Spearman's correlation coefficient were employed, with a significance threshold set at p < 0.05.

We identified increased levels of serum amyloid A (SAA), platelets, and leukocytes solely in male obese patients. We found a noteworthy sex-dependent pattern in regard to inflammatory response: obese boys showed higher TNFβ, IL15, and IL2 and lower IL10 and IL13, while obese girls showed increased TNFα, CCL3, CCL4, and IP10 content in the circulation. BMI Z-score was significantly linearly correlated with neutrophils, leukocytes, platelets, SAA, TNFα, CCL3, CCL4, IP10, and IL13 levels within the entire cohort (non-sex-dependent).

Our data support a complex relationship between adiposity, blood cell count, and circulating inflammatory cytokine content. High SAA levels suggest that this factor may play a critical role in local and systemic inflammation. In the eutrophic group, females presented a lower status of inflammation, as compared to males. Both obese boys and girls showed an increased inflammatory response in relation to eutrophic counterparts. Taken together, results point out to clear sex dimorphism in the inflammatory profile of obese adolescents.