Orlistat Confers Neuroprotection in Traumatic Brain Injury by Modulating Microglial Lipid Metabolism.

ABSTRACT: Traumatic brain injury (TBI) represents a major cause of mortality and disability worldwide, particularly affecting young adults and elderly populations. This study investigates the neuroprotective potential of orlistat (ORL), a gastrointestinal lipase inhibitor, in a murine TBI model. Behavioral, histological, and molecular analyses demonstrated that ORL significantly attenuated TBI-induced neurological damage. Microglial depletion experiments revealed that ORL's neuroprotective effects were largely mediated through microglial modulation. In vitro and in vivo studies showed that ORL suppressed microglial activation, phagocytosis, and migration. Single-cell RNA sequencing identified upregulation of lipoprotein lipase (LPL) in a TBI-induced microglial subpopulation. Molecular docking predic

SUBMITTER: Yu C 

PROVIDER: S-EPMC12468502 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature