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Carriers of the A allele rs2294918 have reduced hepatic PNPLA3 messenger ribonucleic acid (mRNA) and protein levels, suggesting that this variant reduces PNPLA3 expression without affecting adiponutrin enzymatic activity [265]

Indeed, in addition to glutamine production, in our metabolomics experiment, FOXO1 inhibition significantly affected pathways related to ammonia recycling and nitrogen metabolism, such as the urea cycle, glutamate metabolism, arginine and proline metabolism, glycine and serine metabolism (Appendix Fig

Taken together, these heterogeneous findings highlight both biological plausibility and the methodological constraints that shape the current evidence base, motivating the integrative Discussion below

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