Diet-Driven Microglial Activation: Region-Specific Neuroinflammation in the Mouse Brain

Area of Science:

• Neuroscience
• Immunology
• Genomics

Background:

• High-fat diet (HFD) consumption is linked to brain inflammation and neurodegeneration.
• Previous studies showed HFD up to 24 weeks did not increase pro-inflammatory cytokines or impair memory.
• This study investigates neuroimmune responses and microglial activation at the transcriptional level.

Purpose of the Study:

• To examine region- and time-dependent transcriptional changes in the brain induced by HFD.
• To identify specific genes and pathways involved in neuroimmune responses to HFD.
• To assess microglial activation signatures in response to HFD.

Main Methods:

• Male C57BL/6J mice were fed normal diet (ND) or HFD for 4, 12, or 24 weeks.
• Bulk RNA sequencing was performed on four brain regions: cerebellum, hippocampus, hypothalamus, and cortex.
• Analysis focused on differentially expressed genes (DEGs) and pathway enrichment.

Main Results:

• HFD induced region- and time-dependent transcriptional alterations across brain regions.
• The hypothalamus and hippocampus showed significant changes, while cerebellar involvement diminished over time.
• Consistent regulation of three genes (Lcn2, Ch25h, Gimap9) and identification of DEGs linked to microglial activation and inflammation.

Conclusions:

• HFD selectively disrupts brain homeostasis through region-specific transcriptional changes.
• These changes are associated with microglial activation and inflammatory processes.
• NF-κB-related pathways are potential candidates, but require direct mechanistic validation.