Bile acids attenuate PKM2 pathway activation in proinflammatory microglia

Area of Science:

• Neuroscience
• Biochemistry
• Immunology

Background:

• Glycolysis is a key metabolic pathway. Central nervous system (CNS) pathologies involve increased glycolysis and inflammation.
• Pyruvate kinase (PK) has two isoforms, PKM1 and PKM2. PKM2 acts as a transcription factor regulating glycolysis and inflammation.
• Microglia and macrophages drive CNS inflammation after spinal cord injury (SCI). Bile acid receptor TGR5 activation inhibits pro-inflammatory pathways.

Purpose of the Study:

• To investigate how bile acids affect glycolytic enzyme expression and PKM2 regulation in CNS inflammation.
• To explore the therapeutic potential of bile acids in neuroinflammatory conditions.

Main Methods:

• Primary microglial and Raw264.7 macrophage cell cultures were used.
• Cells were stimulated with bacterial lipopolysaccharide (LPS) or subjected to SCI models.
• Expression of PKM1, PKM2, and target genes was analyzed.
• Effects of TUDCA and TLCA pretreatment were evaluated.

Main Results:

• LPS induced PKM1, PKM2, and target gene expression in cell cultures.
• SCI increased PKM2 immunoreactivity in macrophages.
• TUDCA and TLCA reduced PKM2 and target gene expression in cell cultures.
• TUDCA treatment decreased PKM2 expression in the SCI lesion center.

Conclusions:

• PKM2 plays a significant role in the inflammatory response in CNS pathologies.
• Bile acids, including TUDCA and TLCA, can regulate the PKM2 pathway.
• Bile acids represent a novel therapeutic strategy for neuroinflammation by modulating PKM2 activity.