Abstract 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
Wang et al. (Wed,) studied this question.