Scholarlink

Background <p>Nutritional strategies aimed at augmenting growth performance remain a central focus in poultry science. The liver, as a pivotal metabolic organ, exerts profound influence on skeletal muscle development. Nevertheless, the mechanistic interplay between hepatic metabolism and myogenesis has not been fully delineated. Here, by integrating multi-omics analyses with functional validation, we identified xanthosine, a metabolic derivative of hepatic caffeine catabolism, as a previously unrecognized regulator of broiler muscle growth. We further elucidated its mechanistic role in promoting myoblast proliferation.</p> Results <p>Comparative phenotypic assessment of high- and low-body-weight broilers revealed substantial differences in breast muscle mass. Metagenomic profiling of cecal microbiota demonstrated only a limited association between microbial composition and body weight. In contrast, untargeted plasma metabolomics uncovered a systemic upregulation of amino acid metabolism in high-body-weight broilers, concomitant with a pronounced activation of caffeine metabolism. Consistently, hepatic transcriptomic profiling revealed marked induction of cytochrome P450 family 1 subfamily A member 2 (<i>CYP1A2</i>), encoding a key enzyme catalyzing caffeine catabolism. Integrated KEGG pathway enrichment across metabolomic and transcriptomic datasets highlighted caffeine metabolism as a significantly perturbed pathway. Among its downstream metabolites, plasma xanthosine was robustly elevated in high-body-weight broilers. Functional validation via in ovo injection demonstrated that xanthosine administration significantly augmented post-hatch growth performance by increasing skeletal muscle mass. Mechanistic investigations further established that xanthosine drives myoblast proliferation through activation of the ERK/GSK3β/β-catenin signaling cascade.</p> Conclusions <p>Together, these findings delineate a liver–muscle metabolic axis in which hepatic <i>CYP1A2</i>-driven caffeine metabolism elevates circulating xanthosine, which in turn acts as a pivotal molecular effector of myogenic growth. This study uncovers a previously unappreciated metabolic mechanism by which hepatic activity orchestrates skeletal muscle development. It also highlights targeted modulation of xanthosine metabolism as a promising strategy to enhance broiler growth performance and production efficiency.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Liver–muscle metabolic crosstalk: xanthosine as a key effector of broiler myogenesis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月8日

查看全文
  • Yiwei Chen,
  • Cong Ding,
  • Meijuan Ren,
  • Zhixuan Li,
  • Shiqi Liu,
  • Haoming Sun,
  • Sijia Yu,
  • Qiang Niu,
  • Xingyu Li,
  • Bing Li,
  • Li Li,
  • Xiaojun Yang,
  • Qingzhu Sun

摘要

Background

Nutritional strategies aimed at augmenting growth performance remain a central focus in poultry science. The liver, as a pivotal metabolic organ, exerts profound influence on skeletal muscle development. Nevertheless, the mechanistic interplay between hepatic metabolism and myogenesis has not been fully delineated. Here, by integrating multi-omics analyses with functional validation, we identified xanthosine, a metabolic derivative of hepatic caffeine catabolism, as a previously unrecognized regulator of broiler muscle growth. We further elucidated its mechanistic role in promoting myoblast proliferation.

Results

Comparative phenotypic assessment of high- and low-body-weight broilers revealed substantial differences in breast muscle mass. Metagenomic profiling of cecal microbiota demonstrated only a limited association between microbial composition and body weight. In contrast, untargeted plasma metabolomics uncovered a systemic upregulation of amino acid metabolism in high-body-weight broilers, concomitant with a pronounced activation of caffeine metabolism. Consistently, hepatic transcriptomic profiling revealed marked induction of cytochrome P450 family 1 subfamily A member 2 (CYP1A2), encoding a key enzyme catalyzing caffeine catabolism. Integrated KEGG pathway enrichment across metabolomic and transcriptomic datasets highlighted caffeine metabolism as a significantly perturbed pathway. Among its downstream metabolites, plasma xanthosine was robustly elevated in high-body-weight broilers. Functional validation via in ovo injection demonstrated that xanthosine administration significantly augmented post-hatch growth performance by increasing skeletal muscle mass. Mechanistic investigations further established that xanthosine drives myoblast proliferation through activation of the ERK/GSK3β/β-catenin signaling cascade.

Conclusions

Together, these findings delineate a liver–muscle metabolic axis in which hepatic CYP1A2-driven caffeine metabolism elevates circulating xanthosine, which in turn acts as a pivotal molecular effector of myogenic growth. This study uncovers a previously unappreciated metabolic mechanism by which hepatic activity orchestrates skeletal muscle development. It also highlights targeted modulation of xanthosine metabolism as a promising strategy to enhance broiler growth performance and production efficiency.

Graphical Abstract