Lysolecithin Attenuates LPS-Induced Acute Liver Injury in Weaned Piglets by Inhibiting M1 Macrophage Polarization via the mTOR–Glycolysis Pathway

Macrophage polarization is widely recognized as a pivotal role in the maintenance of liver homeostasis. Lysolecithin (LPC) has previously been associated with hepatoprotective effect. This study aimed to determine whether LPC protected against lipopolysaccharide (LPS)-induced liver injury by modulating macrophage polarization. Twenty-four piglets were allocated in a 2 × 2 factorial design, involving dietary supplementation (0 vs. 0.01% LPC) and immunological challenge (saline vs. LPS). Animals were euthanized 4 h post-injection, and liver tissues were harvested for analysis. Our findings showed that LPS challenge induced significant liver damage, which was ameliorated by LPC supplementation, as evidenced by improved histological and functional outcomes. LPC counteracted the LPS-induced dysregulation of mRNA expression related to macrophage polarization, including pro-inflammatory markers (<i>IL-6</i>, <i>IL-1β</i>, <i>TNF-α</i>, <i>IFN-γ</i>, <i>iNOS</i>, and <i>CD80</i>) (<i>p</i> < 0.05). Furthermore, LPC restored the expression of key metabolic genes involved in glycolysis and the TCA cycle (<i>HK2</i> and <i>IDH</i>) (<i>p</i> < 0.05). Mechanistically, LPC normalized the activation of the mTOR signaling pathway by modulating both mRNA and protein levels of mTOR, S6K1, and HIF-1α (<i>p</i> < 0.05). These findings suggest that LPC attenuates LPS-induced liver injury by influencing metabolic and inflammatory pathways, potentially through the inhibiting M1 polarization mediated by glycolysis-related mTOR signaling pathways. Targeting macrophage polarization by LPC may represent a promising therapeutic strategy for inflammatory liver conditions.