Supporting data for "Investigating the vulnerability of neuroinflammation and neurodegeneration by systemic inflammation in zebrafish with high-fat diet"

The research investigates the impact of systemic inflammation on neuroinflammation in an obesity model using zebrafish. Obesity was established by feeding adult and larval zebrafish a tailor-made high-fat diet. The model of high-fat diet-induced obesity was validated through Oil Red-O staining in larvae and adults, body mass index measurements in adults, and BODIPY staining of the liver in larvae.In one experimental model, fin amputation was performed on both obese larvae and adults, while in a second model, intraperitoneal lipopolysaccharide injection was administered to obese adult zebrafish. Neuroinflammation was observed in high-fat diet-induced obese zebrafish larvae and adults. In the model involving fin amputation of obese zebrafish, altered adipokine expression was noted. Additionally, neuroinflammation, increased microglia, and elevated Lipocalin-2 expression in the posterior tuberculum were recorded. Cognitive decline and anxiety-like behavior were observed in obese zebrafish following fin amputation.In the model of obese zebrafish injected intraperitoneally with lipopolysaccharide, altered metabolic pathways, iron accumulation, increased Lipocalin-2 expression, macrophage infiltration in the posterior tuberculum, and neuroinflammation were reported. Autophagy was also investigated. The IL-1β gene was specifically knocked out in macrophages to assess whether its deletion could ameliorate inflammation and neuroinflammation. Results indicated that IL-1β knockout in macrophages led to improved cognition and reduced neuroinflammation following systemic inflammation.Collectively, these data identify macrophage-derived IL-1β as a pivotal mediator connecting systemic inflammation, lipid metabolism, and neuroinflammatory outcomes during obesity. The coordinated suppression of cytokine, adipokine, and iron metabolism disturbances in IL-1β knockout zebrafish underscores the systemic regulatory role of IL-1β. By bridging behavioral, molecular, and imaging analyses, comprehensive evidence is provided that IL-1β-dependent pathways integrate peripheral metabolic inflammation with CNS pathology. These findings highlight IL-1β as a promising therapeutic target for dissociating systemic metabolic inflammation from neurodegenerative risk, advancing the understanding of sex-specific immune–metabolic–neural interactions in obesity and inflammatory disease contexts.