Whispering Through the Barrier: Signaling Interfaces for Peripheral Regulation of Brain Function in Obesity

This review highlights signaling modalities at the blood-brain and blood-cerebrospinal fluid barriers, with reference to the cell types and pathways recruited under steady state conditions and in obesity. We summarize areas of consensus and unresolved questions surrounding the temporal progression of neuroinflammation and the propagation of neuroimmune responses between different cell types and circuits. While data on the reversibility of these changes is scarce, we review the available data on reinstatement of neuroimmune homeostasis following physiological and pharmacological interventions. Published data from preclinical models aligns with evidence implicating middle age as a critical period for the impact of obesity on brain function in humans. Elucidating the metabolic and immune signatures associated with neurological dysfunction could identify novel biomarkers and inform the development of targeted strategies to improve healthspan in obese individuals.