Synergy of genetics and lipid metabolism driving feed utilization efficiency in chickens

Abstract

Residual feed intake (RFI) is a key indicator of feed efficiency, critical for enhancing the economic sustainability of poultry production. However, the genetic and metabolic regulatory mechanisms of RFI remain unclear. This study analyzed the genome, liver transcriptome, metabolome, and lipidome of hens with low and high feed efficiency (N = 60) from the previously established RFI divergent broiler lines (F15). Our results revealed pronounced genetic differentiation between low RFI (LRFI) and high RFI (HRFI) lines and identified genomic signatures of selection associated with feed efficiency. Transcriptomic analysis showed differential expression of genes involved in neural regulation and lipid metabolism. Notably, LRFI chickens exhibited reduced hepatic lipid accumulation, which was associated with decreased fatty acid metabolism and increased cholesterol metabolism (P < 0.05). The lipidomic analysis uncovered distinct profiles of glycerophospholipids (e.g., PE-P and PC-O) and sphingolipids (e.g., ceramides), which were more abundant in LRFI chickens (P < 0.05) and strongly correlated with key lipid metabolism processes (P < 0.05). Despite improved feed efficiency, LRFI chickens demonstrated signs of increased oxidative stress. Moreover, integrative analyses revealed that genes such as MGAT5, GABRA4, and LRRC4C, exhibiting strong selection signatures and higher expression in the LRFI line (P < 0.05), were identified as key regulators of lipid metabolism, potentially contributing to the observed differences in feed efficiency. This comprehensive study highlights the synergistic effect of genetics and lipid metabolism in driving feed utilization efficiency in chickens, establishing a scientific foundation for breeding strategies aimed at improving feed efficiency in poultry production.

Keywords: Chicken; Genetics; Lipid metabolism; Multiomics; RFI.

Fig. 1

Differences in the genetic structure between high and low RFI chickens. (A) RFI values of individuals from the high and low RFI lines. (B) Body weights of individuals from the high and low RFI lines. (C) Liver weight index (liver weight/body weight) of individuals from the high and low RFI lines. The values are the mean ± SEM, * represents P < 0.05. (D) PCA of the RFI population. (E) Neighbor-joining tree analysis of the RFI population. (F) Admixture analysis of the RFI population.

Fig. 2

Genetic selection and differential expression analysis identify important genes. (A) Manhattan plot of Z-Fst for the RFI population, highlighting the top 5 % as significant regions. (B) Manhattan plot of ROH islands for high and low RFI lines, highlighting the top 1 % as significant regions. (C) PCA of samples from high (red) and low (green) RFI lines. (D) Volcano plot of DEGs between high and low RFI lines. Red indicates up-regulated genes, green indicates down-regulated genes. (E) Expression of PSGs in the RFI population (LRFI/HRFI). Asterisks indicate P value < 0.05, and genes in red are both PSGs and DEGs. (F) Enrichment analysis for upregulated and downregulated DEGs between high and low RFI lines.

Fig. 3

Differences in liver metabolites between high and low RFI lines. (A) OPLS-DA score plot of metabolites from high and low RFI line samples. (B) OPLS-DA S-plot. Red points indicate metabolites with VIP > 1, green points denote VIP ≤ 1. (C) Classification and quantity of differential metabolites. (D) Variations in bile acid content between high and low RFI lines (LRFI/HRFI). (E) Levels of free cholesterol (FC), total bile acid (TBA), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) by lipid biochemical analysis. The values are the mean ± SEM, * represents P < 0.05, ** represents P < 0.01 and *** represents P < 0.001. (F) Differential gene expression related to cholesterol transport, steroid biosynthesis and apolipoproteins (LRFI/HRFI). (G) Schematic representation of lipid content and gene expression changes in cholesterol metabolism pathways in the liver of the LRFI line.

Fig. 4

Differences in liver lipid profiles across RFI divergent chickens. (A) Lipid class and quantity detected by lipidomic analysis. (B) OPLS-DA score plot of metabolites in high and low RFI samples. (C) Free fatty acid (FFA) and triglyceride (TG) contents in lipidomic and lipid biochemical analysis. (D) Differential content of FFA between high and low RFI groups (LRFI/HRFI). (E) Differential expression of key genes in lipid metabolism pathways (LRFI/HRFI). (F) GSSG levels in high and low RFI chicken livers. (G) MDA levels in high and low RFI chicken livers. (H) 4-HNE levels in high and low RFI chicken livers. (I) Differential expression of oxidative stress-related genes (LRFI/HRFI). (J) Schematic representation of changes in lipid content and gene expression in fatty acid metabolism pathways in the LRFI chicken livers. The values are the mean ± SEM, * represents P < 0.05, ** represents P < 0.01 and *** represents P < 0.001.

Fig. 5

Important candidate genes and lipids associated with RFI. (A) The relationship between lipid profiles and key candidate genes. Lipid data were obtained from lipidomics and biochemical assays. The heatmap on the right displays the Pearson correlation coefficients between lipid pairs, where red and blue squares represent positive and negative correlations, respectively. The size of each square reflects the absolute value of the correlation coefficient. Lipid names in red or blue indicate positive or negative correlations, respectively, with lipid transport or oxidative stress indicators. The lines on the left represent the correlation between candidate gene expression and lipid content. Orange and blue lines indicate positive and negative correlations, respectively, with line thickness representing the strength of the correlation. Solid lines indicate significant correlations (P value < 0.05), while dashed lines indicate non-significant correlations (P value ≥ 0.05). (B-D) Selection sweep regions near the MGAT5 (B), GABRA4 (C), and LRRC4C (D) genes, and their expression levels in high and low RFI lines using RNA-seq and qRT-PCR. The values are the mean ± SEM, * represents P < 0.05, ** represents P < 0.01 and *** represents P < 0.001.