Modulation of liver cholesterol homeostasis by choline supplementation during fibrosis resolution

Liver fibrosis is a critical global health challenge, often leading to severe liver diseases without timely intervention. Choline deficiency has been linked to metabolic dysfunction associated steatohepatitis (MASH) and liver fibrosis, suggesting choline supplementation as a potential therapeutic approach. This study aimed to explore the therapeutic potential of choline supplementation in liver fibrosis resolution and its effects on cholesterol homeostasis using a mouse model with induced liver fibrosis. Our findings reveal that choline supplementation significantly decreases blood lactate dehydrogenase (LDH) and non-high-density lipoprotein cholesterol (non-HDL-C) levels. Transcriptome analysis showed that choline supplementation primarily induces genes related to cholesterol homeostasis, suggesting a significant impact on liver cholesterol synthesis. However, choline supplementation did not significantly alter the expression of fibrosis-related, choline metabolism-related, or epigenetics-related genes. This study provides novel insights into the role of choline in liver health and cholesterol metabolism, potentially informing treatments for liver fibrosis and related conditions.