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The CD98 transporter system (SLC7A5/SLC3A2) mediates the entry of leucine and other BCAAs into cells, which can drive mTORC1 activation and enhance glycolytic metabolism, thereby promoting the expression of pro-inflammatory genes such as IL-1β, TNF-α, and C-X-C motif chemokine ligand 10 (CXCL10) ( Overall, the role of BCAA metabolism in macrophage polarization is more appropriately defined as an “integrative module of nutrient sensing and energy metabolism,” and its biological output is jointly influenced by dose, metabolic state, inflammatory stage, and the tissue microenvironment
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