Dietary glucuronolactone alleviates hepatic lipid accumulation via the enterohepatic axis in laying hens

Abstract Background For laying hens in the late stage of peak production, dysregulated liver lipids are one of the leading causes of declining egg production. Glucuronolactone (D-Glu) is used as a functional beverage additive in human food products and has been reported to play a role in lipid metabolism. However, its use with laying hens is rarely reported. This study integrated in vitro avian hepatocyte culture (LMH) models and in vivo laying hen trials to investigate the regulatory effects of D-Glu on hepatic lipid deposition. Results D-Glu significantly reduced intracellular lipid deposition in hepatocytes both in vivo and in vitro models, while also improving the production performance of laying hens. Liver lipidomic profiling revealed that D-Glu supplementation increased hepatic phospholipid abundance and reduced triglyceride (TG) accumulation, particularly by decreasing TG species enriched with polyunsaturated fatty acid (PUFA). This reduction in hepatic lipids is achieved by downregulating genes associated with fatty acid (FA) synthesis ( FASN , ACSL , and PPAR-γ ) and transport ( FABP1 and CD36 ) pathways in the liver. Notably, D-Glu administration modulated the relative abundance of specific bacteria, particularly Bacteroides , CHKCI001 , and Angelakisella , during hepatic lipid reduction mediation. Furthermore, D-Glu modified the composition of FA in the yolk, increasing the deposition of PUFA. Correlation analyses strongly supported the involvement of the enterohepatic axis in the lipid-lowering mechanism of D-Glu. Conclusion D-Glu mediates lipid redistribution via the enterohepatic axis, effectively reducing hepatic lipid deposition while promoting the deposition of PUFA in egg yolk, ultimately alleviating the decline in production performance during the late peak laying period. Graphical Abstract