Abstract
Disclosure: G. Scozia: None. D. Menghini: None. D. Fintini: None. S. Cianfarani: None. V. Russo: None. M. Mainardi: None. N. Gianni: None. G. Furini: None. G. Scabia: None. M. Maffei: None. M. Manco: None. Background: In pediatric obesity, altered energy regulation and impaired inhibitory control over food intake are linked to dysfunction in the dorsolateral prefrontal cortex (DLPFC). Lifestyle interventions can potentially restore these brain-metabolic pathways. Leptin, brain-derived neurotrophic factor (BDNF), and eotaxin (CCL11), a chemokine involved in immune signaling, may modulate neural responses to metabolic challenges. Objective: To assess the impact of an 8-week intensive health behavioral treatment (IHBT) on DLPFC activation during oral glucose tolerance testing (OGTT), and to explore the relationship with insulin sensitivity and circulating levels of leptin, BDNF and eotaxin in children with obesity. Methods: Twenty-seven children with obesity (mean age 11 years) underwent functional near-infrared spectroscopy (fNIRS) during OGTT at baseline (T0) and post-IHBT (T1). The IHBT included healthy diet, structured physical activity, and cognitive training. Changes in cerebral blood flow (total Hb, tHb) and oxygenated hemoglobin (O₂Hb) were measured in the DLPFC. Insulin sensitivity was assessed via the Matsuda Index and HOMA-IR; serum eotaxin, leptin, and BDNF levels were also measured by commercial assays. Results: After IHBT, there was a significant increase in bilateral DLPFC activation during OGTT: Left DLPFC: ΔO₂Hb ↑, p < 0.01. Right DLPFC: ΔO₂Hb ↑, p < 0.05. ΔtHb bilateral ↑, indicating enhanced cortical perfusion. Improvement in DLPFC activity correlated with metabolic indices: Positive correlation with Matsuda Index (r = 0.54, p < 0.01). Negative correlation with HOMA-IR (r = -0.47, p < 0.05). Left DLPFC activation at T1 showed sex-related differences, with greater increase in males (p < 0.05). Baseline eotaxin levels were positively associated with DLPFC activation changes at T1 (r = 0.41, p < 0.05), while leptin and BDNF showed no significant associations. Conclusion: An 8-week lifestyle intervention significantly enhanced DLPFC activation during glucose challenge, suggesting improved neural regulation of food-related behavior in children with obesity. The association with eotaxin implicates a potential neuroimmune mechanism whereby inflammatory signaling may influence prefrontal responsiveness to metabolic inputs. Eotaxin may serve as a biomarker of neuroplastic adaptation to behavioral interventions targeting obesity. Presentation: Monday, July 14, 2025