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Serum proteomics and biomarker discovery across the spectrum of nonalcoholic fatty liver disease

4.3 Glutamine Glutamine (Gln) is mainly converted through GLS/glutamate dehydrogenase (GLUD)-related reactions to generate -KG, which enters the TCA cycle and provides anaplerotic substrates for oxidative metabolism, while also influencing polarization-related epigenetic regulatory processes through metabolic ratios such as -KG/succinate ( Glutamine (Gln) metabolism in macrophage polarization is mainly manifested as a composite regulatory axis of TCA cycle anaplerosis-mitochondrial metabolism-epigenetic coupling. Its role is usually not reflected by the output of a single effector molecule, but rather by the coordinated shaping of polarization-related transcriptional programs through metabolic flux and key intermediates, particularly -KG ( -KG is considered a key hub linking Gln metabolism to phenotypic remodeling ( It should be noted that the effects of Gln metabolism on polarization direction are markedly context-dependent

Caption: MOTS-c is a mitochondrial-derived peptide that translocates to the nucleus under metabolic stress, activating AMPK-dependent pathways that enhance glucose metabolism, fatty acid oxidation, and mitochondrial biogenesisthe core metabolic adaptations of endurance training

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