Alterations in one-carbon metabolism in metabolic dysfunction associated steatotic liver disease may be modified by semaglutide

Alterations in one-carbon metabolism were observed in 100 patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

• Changes in folate, vitamin B6, betaine, serine, and glycine concentrations suggest disruptions in metabolic pathways related to one-carbon metabolism.
• Increased levels of metabolites associated with the conversion of homocysteine and elevated glutamate were noted in MASLD patients.
• Corresponding changes in the activity of key enzymes involved in these metabolic pathways were identified.
• Similar metabolic alterations were found in a mouse model of diet-induced obesity and steatohepatitis treated with semaglutide.
• Semaglutide treatment resulted in reductions in body weight, liver inflammation, and fibrosis in mice, reversing observed metabolic and gene expression changes.

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