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

**Authors:** Yiru Shen, Jinglong Chen, Yunqi Xiao, Shourong Shi

PMC · DOI: 10.1186/s40104-025-01350-2 · 2026-03-05

## TL;DR

Glucuronolactone reduces liver fat in laying hens and improves egg production by affecting gut-liver interactions and fat metabolism.

## Contribution

This study is the first to show that glucuronolactone reduces hepatic lipid accumulation in laying hens via the enterohepatic axis.

## Key findings

- Glucuronolactone reduced liver lipid accumulation and improved laying hens' production performance.
- D-Glu increased phospholipids and decreased triglycerides enriched with polyunsaturated fatty acids in the liver.
- D-Glu modulated gut bacteria like Bacteroides and Angelakisella, linking gut health to liver lipid regulation.

## Abstract

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.

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.

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.

The online version contains supplementary material available at 10.1186/s40104-025-01350-2.

## Linked entities

- **Genes:** FASN (fatty acid synthase) [NCBI Gene 2194], Acsl (Acyl-CoA synthetase long-chain) [NCBI Gene 46068], PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468], FABP1 (fatty acid binding protein 1) [NCBI Gene 2168], CD36 (CD36 molecule (CD36 blood group)) [NCBI Gene 948]
- **Chemicals:** glucuronolactone (PubChem CID 92283), triglyceride (PubChem CID 5460048)
- **Species:** Gallus gallus (taxon 9031)

## Full-text entities

- **Genes:** FASN (fatty acid synthase) [NCBI Gene 396061], FABP1 (fatty acid binding protein 1) [NCBI Gene 374015] {aka L-FABP, LFABP}, ACTB (actin, beta) [NCBI Gene 396526] {aka Bact, actin}, PNPLA2 (patatin like phospholipase domain containing 2) [NCBI Gene 431066] {aka ATGL}, PPARG (peroxisome proliferator-activated receptor gamma) [NCBI Gene 373928] {aka PPARgamma, PPARgamma2}, INS (insulin) [NCBI Gene 396145]
- **Diseases:** hepatic (MESH:D056486), hypoxic (MESH:D002534), adiposity (MESH:D018205), obesity (MESH:D009765), type 2 diabetes mellitus (MESH:D003924), FLS (MESH:D005234), lipid (MESH:D011017), hepatocellular carcinoma (MESH:D006528), metabolic disorders (MESH:D008659), hepatic lipidosis (MESH:D008064), disorders of lipid metabolism (MESH:D052439), PCoA (MESH:D001259), FA (MESH:D008067), inflammation (MESH:D007249), liver disease (MESH:D008107)
- **Chemicals:** Oil Red O (MESH:C011049), vitamin A (MESH:D014801), heptadecanoic acid (MESH:C013102), I (MESH:D007455), vitamin B12 (MESH:D014805), N-carbamoylglutamate (MESH:C006895), TRIzol (MESH:C411644), DCF (MESH:C037631), 2',7'-dichlorofluorescein diacetate (MESH:C029569), Fe (MESH:D007501), glycogen (MESH:D006003), Lipid (MESH:D008055), stearic acid (MESH:C031183), arachidonic acid (MESH:D016718), PA (MESH:D019308), chloroform (MESH:D002725), Co (MESH:D003035), linolenic acid (MESH:D017962), calcium pantothenate (MESH:D010205), phospholipid (MESH:D010743), water (MESH:D014867), CCK-8 (MESH:D012844), phosphoethanolamine (MESH:C005448), ROS (MESH:D017382), folic acid (MESH:D005492), sulfuric acid (MESH:C033158), ceramide (MESH:D002518), calcium (MESH:D002118), monoglycerides (MESH:D050178), short-chain FA (MESH:D005232), cholesterol (MESH:D002784), Mn (MESH:D008345), D-Glucose (MESH:D005947), glutamic acid (MESH:D018698), DG (MESH:D004075), isopropanol (MESH:D019840), eicosenoic acid (MESH:C572289), Cu (MESH:D003300), sphingolipids (MESH:D013107), oleic acid (MESH:D019301), sciadonic acid (MESH:C045533), vitamin B6 (MESH:D025101), biotin (MESH:D001710), glucuronic acid (MESH:D020723), glycerol (MESH:D005990), Zn (MESH:D015032), phosphorus (MESH:D010758), GP (MESH:D020404), PUFA (MESH:D005231), n-hexane (MESH:C026385), acids (MESH:D000143), ammonium formate (MESH:C030544), PE (MESH:C483858), vitamin K3 (MESH:D024483), C18:2n6 (MESH:D019787), methanol (MESH:D000432), ethanolamine (MESH:D019856), fat (MESH:D005223), C18 FA (-), C22:5n6 (MESH:C026219)
- **Species:** Bacillota (clostridial firmicutes, phylum) [taxon 1239], Mycoplasma (genus) [taxon 2093], Gallus gallus (bantam, species) [taxon 9031], Angelakisella (genus) [taxon 1935176], Homo sapiens (human, species) [taxon 9606], Bifidobacterium (genus) [taxon 1678], Fusobacterium (genus) [taxon 848], Mus musculus (house mouse, species) [taxon 10090], Bacteroides (genus) [taxon 816], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** LMH — Gallus gallus (Chicken), Chicken hepatoma, Cancer cell line (CVCL_2580)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12961837/full.md

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Source: https://tomesphere.com/paper/PMC12961837