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

## TL;DR

Lysolecithin reduces liver damage in piglets caused by bacterial toxins by inhibiting harmful immune responses and improving liver metabolism.

## Contribution

This study reveals that lysolecithin protects the liver by modulating macrophage polarization and the mTOR–glycolysis pathway.

## Key findings

- Lysolecithin supplementation ameliorates LPS-induced liver injury in piglets.
- Lysolecithin inhibits M1 macrophage polarization by modulating the mTOR–glycolysis pathway.
- Lysolecithin restores metabolic gene expression related to glycolysis and the TCA cycle.

## Abstract

Liver injury poses a significant health burden and is frequently initiated by bacterial infections. This study examined whether lysolecithin—a natural bioactive lipid—could confer hepatoprotection against bacterial toxin-induced damage by modulating macrophage activity. Using a weaned piglet model, we assessed the effects of dietary lysolecithin supplementation in animals challenged with lipopolysaccharide. Results indicated that lysolecithin significantly attenuated lipopolysaccharide-induced liver injury, improved hepatic histopathology and function, restored immune cell homeostasis, and optimized cellular energy metabolism. Moreover, lysolecithin was found to regulate a key intracellular signaling pathway involved in macrophage polarization. Collectively, these findings suggest that lysolecithin alleviates liver injury by fine-tuning immune responses and metabolic pathways. This study holds translational relevance, offering novel perspectives for developing potential hepatoprotective agents or therapeutic strategies against liver-related diseases.

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 (IL-6, IL-1β, TNF-α, IFN-γ, iNOS, and CD80) (p < 0.05). Furthermore, LPC restored the expression of key metabolic genes involved in glycolysis and the TCA cycle (HK2 and IDH) (p < 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 (p < 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.