The Regulatory Role of FABP4 in Microbiome-Brain-Gut Communication Under High-Fat-Diet Conditions.

High-fat diets (HFDs) are major environmental factors influencing metabolic homeostasis, immune regulation, and brain function, largely through their effects on gut microbiota and intestinal barrier integrity. Disruption of the microbiome-brain-gut axis has been increasingly implicated in systemic and neuroinflammatory processes; however, the molecular mediators that integrate dietary lipid signals with microbial and host responses remain incompletely defined. This review synthesizes the current evidence on the role of fatty acid-binding protein 4 (FABP4) as an integrative node linking HFD-induced gut dysbiosis to systemic and central inflammatory signaling. We critically evaluated experimental and translational studies addressing HFD-driven alterations in gut microbiota composition, intestinal barrier function, and inflammatory pathways, with particular emphasis on FABP4-mediated mechanisms across epithelial, immune, and neural compartments. The available data indicate that FABP4 responds to dietary and microbiome-derived cues and contributes to coordinated metabolic and inflammatory responses, affecting both peripheral tissues and the central nervous system. These findings support a model in which FABP4 participates in diet-driven feedback loops that amplify gut barrier dysfunction, immune activation, and neuroinflammation. In conclusion, FABP4 emerges as a central molecular mediator within the microbiome-brain-gut axis under HFD conditions, highlighting its potential relevance in understanding the pathophysiology of metabolic and neuroinflammatory disorders and guiding future integrative research strategies.