Microglial Ffar4 deficiency promotes cognitive impairment in the context of metabolic syndrome.

ABSTRACT: Metabolic syndrome (MetS) is closely associated with an increased risk of dementia and cognitive impairment, and a complex interaction of genetic and environmental dietary factors may be implicated. Free fatty acid receptor 4 (Ffar4) may bridge the genetic and dietary aspects of MetS development. However, the role of Ffar4 in MetS-related cognitive dysfunction is unclear. In this study, we found that Ffar4 expression is down-regulated in MetS mice and MetS patients with cognitive impairment. Conventional and microglial conditional knockout of Ffar4 exacerbated high-fat diet (HFD)-induced cognitive dysfunction and anxiety, whereas microglial Ffar4 overexpression improved HFD-induced cognitive dysfunction and anxiety. Mechanistically, we found that microglial Ffar4

SUBMITTER: Wang W 

PROVIDER: S-EPMC10836723 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature