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Background <p>The phenomenon where excessive activation of branched-chain amino acid (BCAA) degrading enzymes caused by high concentrations of leucine (Leu) leads to a decrease in the overall concentration of BCAA [including isoleucine (Ile) and valine (Val)] is called BCAA antagonism. Although this phenomenon has long been widely studied, the specific mechanism of its occurrence is still poorly understood. In this study, we investigated the specific mechanism by which Val and Ile alleviate the antagonistic effect caused by high concentrations of Leu through influencing insulin function. First, the ratios of Ile and Val in the low-protein diet were adjusted up and down by 15% to observe the metabolic status of broilers at the end of the experiment (the experiment period was from 0 to 42&#xa0;d). Subsequently, the physiological and biochemical changes related to antagonism were determined using transcriptome and lipid metabolome analyses.</p> Results <p>When fed with a high concentration of Leu, restricting Ile or supplementing Val can effectively alleviate antagonism. Under conditions of excessive dietary Val supplementation, insulin levels remained stable, whereas blood glucose levels increased (<i>P</i> &lt; 0.05), and liver fat accumulated predominantly as ceramides rather than triglycerides, thereby disrupting the insulin-mediated phosphatidylinositol 3-kinase/protein kinase B signaling pathway (<i>P</i> &lt; 0.05). Excessive dietary Ile promoted liver inflammation and interleukin-6 release (<i>P</i> &lt; 0.05), which acted on the pancreas to enhance insulin secretion. Additionally, the glucagon content in the pancreas decreased (<i>P</i> &lt; 0.05), while insulin and glucagon-like peptide-1 levels increased (<i>P</i> &lt; 0.05).</p> Conclusion <p>Supplementation of Val or restriction of Ile in low-protein diets could alleviate the BCAA antagonism caused by high Leu, which mainly achieved by influencing insulin function. These findings provide new insights in revealing the BCAA antagonism.</p> Graphical Abstract <p></p>

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Isoleucine and valine regulate the BCAA antagonism by influencing insulin function in broiler chickens

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月11日

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  • Bin Wang,
  • Xiaodan Zhang,
  • Guang Li,
  • Mingkun Gao,
  • Yuqing Feng,
  • Yong He,
  • Yuming Guo

摘要

Background

The phenomenon where excessive activation of branched-chain amino acid (BCAA) degrading enzymes caused by high concentrations of leucine (Leu) leads to a decrease in the overall concentration of BCAA [including isoleucine (Ile) and valine (Val)] is called BCAA antagonism. Although this phenomenon has long been widely studied, the specific mechanism of its occurrence is still poorly understood. In this study, we investigated the specific mechanism by which Val and Ile alleviate the antagonistic effect caused by high concentrations of Leu through influencing insulin function. First, the ratios of Ile and Val in the low-protein diet were adjusted up and down by 15% to observe the metabolic status of broilers at the end of the experiment (the experiment period was from 0 to 42 d). Subsequently, the physiological and biochemical changes related to antagonism were determined using transcriptome and lipid metabolome analyses.

Results

When fed with a high concentration of Leu, restricting Ile or supplementing Val can effectively alleviate antagonism. Under conditions of excessive dietary Val supplementation, insulin levels remained stable, whereas blood glucose levels increased (P < 0.05), and liver fat accumulated predominantly as ceramides rather than triglycerides, thereby disrupting the insulin-mediated phosphatidylinositol 3-kinase/protein kinase B signaling pathway (P < 0.05). Excessive dietary Ile promoted liver inflammation and interleukin-6 release (P < 0.05), which acted on the pancreas to enhance insulin secretion. Additionally, the glucagon content in the pancreas decreased (P < 0.05), while insulin and glucagon-like peptide-1 levels increased (P < 0.05).

Conclusion

Supplementation of Val or restriction of Ile in low-protein diets could alleviate the BCAA antagonism caused by high Leu, which mainly achieved by influencing insulin function. These findings provide new insights in revealing the BCAA antagonism.

Graphical Abstract