Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury

Abstract

The liver is an exclusive organ with tremendous regenerative capacity. Liver metabolic functions exhibit spatial heterogeneity, reflecting liver zonation. The mechanisms controlling the proliferation of hepatocytes and the accompanying matrix reconstruction during regeneration have been well explored, but the recovery potential of differentiated metabolic functions and zonation after liver injury remains unclear. We employed a mouse model of carbon tetrachloride (CCl4) induced-acute liver injury with clodronate-induced macrophage depletion to clarify the impact of liver injury on liver metabolism and recovery dynamics of metabolic function and liver zonation during regeneration. Depleting macrophages suppressed tissue remodelling and partially delayed cell proliferation during regeneration after liver injury. In addition, recovery of metabolic functions was delayed by suppressing the tissue remodelling caused by the depleted macrophages. The model revealed that drug metabolic function was resilient against the dysfunction caused by liver injury, but glutamine synthesis was not. Metabolomic analysis revealed that liver branched-chain amino acid (BCAA) and carbohydrate metabolism were suppressed by injury. The plasma BCAA concentration reflected recovery of hepatic function during regeneration. Our study reveals one aspect of the regenerative machinery for hepatic metabolism following acute liver injury.

Jian Gan powder ameliorates immunological liver injury in mice by modulating the gut microbiota and metabolic profiles

“…Arginine supplementation is known to reduce liver injury [55,56]. The serum levels of arginine decrease in patients with acute liver injury [57,58]. Therefore, blood arginine is a good indicator of liver regeneration after acute liver damage [57][58][59].…”

“…The serum levels of arginine decrease in patients with acute liver injury [57,58]. Therefore, blood arginine is a good indicator of liver regeneration after acute liver damage [57][58][59]. These ndings suggest that arginine biosynthesis mediates the hepatoprotective effect of JGP.…”

Serum metabolomics strategy for investigating the hepatotoxicity induced by different exposure times and doses of Gynura segetum (Lour.) Merr. in rats based on GC-MS

“…17 Valine is a kind of branched-chain amino acid, which was reported to be crucial for the prevention of liver injury. 34,35 A recent study 36 demonstrated that Ganfule capsule (GFL) might play the protective effect on liver fibrosis by valine biosynthesis. Serine is important in cellular metabolic processes that link glycolysis with one-carbon metabolism to keep redox balance and proliferation.…”

Study of Water- and Organic-Soluble Extracts from Trichosanthes on Type 1 Diabetes Mellitus

“…Upon removal, the liver and skeletal muscles of each rat were immediately fixed in 4% formaldehyde. After routine paraffin embedding, the sample was cut into 5 μ m sections and stained with periodic acid-silver (PAS) for the detection of histopathological alterations and glycogen changes [ 19 ].…”