<b>Clostridium_butyricum</b><b> and butyrate ameliorate obesity</b>

Leveraging EGR1 macrophage-specific differentially expressed genes, both in silico knockout of EGR1 and pharmacological inhibition (EGR1i;IT25) confirmed the functional involvement of PI3K-Akt signaling downstream of EGR1. Integrating metagenomic and single-cell data, we propose a conserved LPS-EGR1 axis that governs macrophage polarization in obesity. To experimentally validate this model, we established an LPS-potentiated HFD-induced obesity model in mice and an LPS-induced M1 polarization model in RAW264.7 macrophages.

Treatment with C. butyricum, butyrate, arginine, or EGR1i significantly attenuated weight gain, downregulated EGR1 expression, and effectively suppressed M1 macrophage polarization, thereby restoring the M1/M2 balance. Notably, this process is accompanied by significant alterations in genes related to the PI3K-Akt signaling pathway, suggesting that this pathway may act in concert with EGR1 within this regulatory network.

In summary, these cross-species experiments elucidate a fundamental mechanism whereby gut-derived LPS regulates macrophage polarization via EGR1. thereby linking microbial dysbiosis to metabolic inflammation in mammals.</p>