Broiler Liver Metabolism Shifts Dramatically With Age, Revealing Fat-Regulating Genes
Integrated metabolomics and transcriptomics map how chicken liver lipid metabolism transforms across five growth stages, pinpointing key regulatory genes.
Summary
Researchers combined non-targeted metabolomics and RNA sequencing to track hepatic metabolism in female broiler chickens at 60, 90, 120, 150, and 180 days of age. From 1,121 identified metabolites, lipid-related compounds showed the most dramatic age-dependent shifts, with oil red O staining confirming escalating lipid droplet accumulation over time. Key metabolic pathways enriched with age included alpha-linolenic acid metabolism, linoleic acid metabolism, and steroid hormone biosynthesis. Transcriptomic analysis identified 12 lipid-metabolism-related genes showing continuously increasing expression, with six standouts—FADS2, ACAT2, APOV1, VTG1, MBOAT2, and ELOVL1—strongly correlated with differential lipid metabolites. These findings illuminate molecular mechanisms underlying hepatic fat deposition in poultry and suggest potential biomarkers for managing fat accumulation in commercial chicken production.
Detailed Summary
Understanding how fat accumulates in poultry livers is commercially and scientifically critical, since the chicken liver is responsible for over 70% of de novo fatty acid synthesis. Unlike mammals, chickens rely almost entirely on the liver—not adipose tissue—to produce fatty acids, which are then packaged into VLDL and transported to muscle and fat depots. Excessive abdominal fat hurts consumer acceptance, while intramuscular fat improves meat quality, making precise control of lipid metabolism a key breeding goal.
This study used female Daheng broilers (n=200) sampled at five time points—60, 90, 120, 150, and 180 days—spanning market age through sexual maturity. Liver tissues underwent LC-MS/MS-based untargeted metabolomics (identifying 1,121 metabolites across positive and negative ion modes) alongside RNA-Seq transcriptomics mapped to the GRCg6a chicken reference genome. Histological staining with H&E and oil red O confirmed progressive hepatocyte enlargement and escalating lipid droplet accumulation with age, validating the biological relevance of molecular findings.
Metabolomic trend analysis revealed that lipid-related metabolites exhibited the most pronounced age-dependent changes, followed by carbohydrate and amino acid metabolites. KEGG pathway enrichment highlighted alpha-linolenic acid metabolism, linoleic acid metabolism, steroid hormone biosynthesis, 2-oxocarboxylic acid metabolism, and nicotinate/nicotinamide metabolism as the most significantly shifting pathways across age groups. OPLS-DA models cleanly separated samples by age, confirming robust stage-specific metabolic signatures.
Transcriptomic analysis using STEM temporal profiling identified 12 lipid-metabolism-related genes with continuously increasing expression trajectories. Pearson correlation analysis integrating differential lipid metabolites and DEGs identified six candidate genes as particularly influential: FADS2 (fatty acid desaturation), ACAT2 (cholesterol and ketone body metabolism), APOV1 and VTG1 (yolk lipid transport), MBOAT2 (lysophospholipid acylation), and ELOVL1 (very long-chain fatty acid elongation). These genes collectively suggest that hepatic lipid metabolism in aging broilers involves not just de novo synthesis but increasingly complex remodeling of fatty acid chain length and unsaturation, as well as lipid transport machinery.
While this study focused on a single commercial broiler breed and female birds only, it provides one of the most comprehensive longitudinal metabolomic-transcriptomic maps of chicken hepatic lipid metabolism to date. The identified gene-metabolite correlations offer actionable targets for breeding programs or nutritional interventions aimed at optimizing fat deposition profiles in commercial poultry.
Key Findings
- 1,121 hepatic metabolites identified across five age stages, with lipid metabolites showing the largest age-dependent shifts.
- Oil red O staining confirmed progressive lipid droplet accumulation in liver from 60 to 180 days of age.
- Key enriched pathways included alpha-linolenic acid, linoleic acid metabolism, and steroid hormone biosynthesis.
- 12 lipid-metabolism genes showed continuously increasing expression; FADS2, ACAT2, APOV1, VTG1, MBOAT2, and ELOVL1 were top candidates.
- Integrated metabolomic-transcriptomic analysis revealed stage-specific molecular signatures linked to hepatic fat deposition.
Methodology
Female Daheng broilers (n=200) were sampled at 60, 90, 120, 150, and 180 days; liver tissues underwent LC-MS/MS untargeted metabolomics and RNA-Seq transcriptomics. Differential metabolites were identified by OPLS-DA (VIP>1, FC≥1.5 or ≤0.667, p<0.05); DEGs were filtered by FDR<0.05 using DESeq2, with qRT-PCR validation of selected genes.
Study Limitations
Study used only female birds of a single commercial broiler breed, limiting generalizability across sexes and breeds. Sample sizes per time point (n=9) are modest for metabolomic studies. Correlations between genes and metabolites are associative; functional validation through gene knockdown or overexpression was not performed.
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