Lipid metabolism orchestrates liver regeneration: an integrated metabolic network

作者：Lian Duan, Yushun Chang, Jinyao Dai, Hui‐Hu Lu, Weijun Zhao, Yuxuan Shen, Jie Lin, Xiujun Cai · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-07232-5 · 被引用次数：21 · 研究领域：Lipid metabolism and biosynthesis、Liver Disease Diagnosis and Treatment、Endoplasmic Reticulum Stress and Disease

Liver regeneration is a tightly regulated biological process driven by the dynamic interplay of lipid metabolism, involving spatially and temporally coordinated pathways of synthesis, degradation, and lipophagy. This comprehensive review delineates the pivotal roles of lipid metabolic networks in liver regeneration and highlights their potential for clinical translation. During the priming phase, transient regenerative-associated steatosis (TRAS) serves important physiological roles which provide energy through β-oxidation and supply substrates for membrane phospholipid biosynthesis, with its regulation orchestrated by transcriptional and post-translational mechanisms. In contrast, chronic lipid dyshomeostasis impairs regeneration through mechanisms including endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and pro-inflammatory signaling. However, protective lipid-handling processes remain active and play pivotal roles in maintaining cellular homeostasis. Lipophagy-mediated selective degradation of lipid droplets (LDs) releases free fatty acids (FFAs), which mitigate oxidative stress and preserve hepatocellular integrity. Furthermore, the gut-liver axis modulates regeneration through microbiota-derived metabolites and incretin hormones that fine-tune the equilibrium between lipid mobilization and storage. Macrophage polarization-metabolic crosstalk emerges as a critical regulator, whereby PPARγ-driven lipogenic networks in reparative macrophages coordinate growth...