Lina Ma

Background: While the growth-immunity trade-off has been extensively studied in plant biology, its existence, underlying immunometabolic mechanisms, and practical implications in animals remain poorly characterized. Chronic immune activation diverts essential bioenergetic resources away from somatic development, highlighting a critical need for interventions capable of modulating this physiological balance. The potent anti-inflammatory properties of 18β-glycyrrhetinic acid (GA), an active component of licorice, provide a unique opportunity to elucidate this regulatory mechanism. Methods: To elucidate the regulatory logic of this trade-off in ruminants, we integrated large-scale physiological profiling, multi-tissue bulk transcriptomics, single-cell RNA sequencing (scRNA-seq), limited proteolysis-coupled mass spectrometry (LiP-MS), and molecular docking. We evaluated a large lamb cohort (n = 448) to determine the systemic and molecular effects of maternal 18β-glycyrrhetinic acid (GA) supplementation on offspring. Results: Gestational GA administration significantly dampened systemic inflammatory tone and oxidative stress, redirecting metabolic resources to somatic growth. This resulted in marked improvements in offspring birth weight (by 7.09%), weaning weight (by 10.66%), skeletal muscle fiber development, and secondary hair follicle maturation. Inter-tissue communication analysis pinpointed the lymph node as the primary signaling hub for GA-mediated inter-organ regulation. Specifically, scRNA-seq revealed that GA preferentially acts on adaptive T-cell subpopulations within the lymph nodes. Furthermore, LiP-MS and molecular docking identified key NF-κB pathway components—specifically PARP1, DDX1, RIPK1, HSPA1A, FLOT1, FLNA, REL, and TRADD—as direct physical binding targets of GA. By engaging these molecular targets, GA suppresses hyperactivated NF-κB signaling in T cells, reducing pro-inflammatory cytokine production and the bioenergetic costs of immune maintenance. Conclusion: This study establishes the operational animal growth-immunity trade-off paradigm and demonstrates that maternal GA intervention successfully optimizes livestock growth performance and systemic homeostasis through precise immunometabolic regulation.

The Chinese Tan sheep is a unique breed of sheep that is typical throughout China, mainly used for fur and meat production. They are widely distributed in northwestern China and are famous for their lambskin and shiny white curly wool. In this study, the phenotypic traits of wool length, birth weight, and head coat color were evaluated in 256 Chinese Tan sheep breeds. Whole genome sequencing generated 23.67 million high-quality SNPs for genome-wide association studies (GWAS). We identified 208 significant SNPs associated with birth wool length, implicating RAD50, MACROD2, SAMD5, SASH1, and SPTLC3 as potential candidate genes for this trait. For birth weight, 1056 significant SNPs, with 76.89% of them located on chromosome 2, were identified by GWAS, and XPA, INVS, LOC121818504, GABBR2, LOC101114941, and LOC106990096 were identified as potential candidate genes for birth weight. The GWAS for head coat color identified 1424 significant SNPs across three chromosomes, with 99.65% on chromosome 14, and SPIRE2, TCF25, and MC1R as candidate genes were found to be possibly involved in the development of the black-headed coat color in sheep. Furthermore, we selected head coat color as a representative trait and performed an independent test of our GWAS findings through multiplex PCR SNP genotyping. The findings validated five mutation sites in chromosome 14 (14,251,947 T>A, 14,252,090 G>A, 14,252,158 C>T, 14,252,329 T>G, and 14,252,464 C>T) within the exon1 of the MC1R gene (517 bp), as identified by GWAS in an additional 102 Tan sheep individuals, and revealed that black-headed sheep predominantly exhibited heterozygous genotypes, possibly contributing to their color change. Our results provide a valuable foundation for further study of these three economically important traits, and enhance our understanding of genetic structure and variation in Chinese Tan sheep.

Fat-tail sheep exhibit a unique trait whereby substantial adipose tissue accumulates in the tail, a phenotype that is advantageous in many agroecological environments. In this study, we conducted histological assays, transcriptome analysis and functional assays to examine morphogenesis, characterize gene expression, and elucidate mechanisms that regulate fat tail development. We obtained the microstructure of tail before and after fat deposition, and demonstrated that measurable fat deposition occurred by the 80-day embryo (E80) stage, earlier than other tissues. Transcriptome profiling revealed 1,058 differentially expressed genes (DEGs) with six markedly different expression trends. GSEA enrichment and other downstream analyses showed important roles for genes and pathways involving in metabolism and that mitochondrial components were specifically overexpressed in the fat tail tissue of the 70-day embryo (E70). One hundred and eighty-three genes were further identified by leading edge gene analysis, among which, 17 genes have been reported in previous studies, including EEF1D, MTFP1, PPP1CA, PDGFD. Notably, the MTFP1 gene was highly correlated with the expression of other genes and with the highest enrichment score and gene expression change. Knockdown of MTFP1 in isolated adipose derived stem cells (ADSCs) inhibited cell proliferation and migration ability, besides, promoted the process of adipogenesis in vitro.