This is a preview of subscription content, access via your institution
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Zhang, Z. et al. Serine catabolism generates liver NADPH and supports hepatic lipogenesis. Nat. Metab. 3, 1608–1620 (2021).
Jin, E. S., Lee, M. H., Murphy, R. E. & Malloy, C. R. Pentose phosphate pathway activity parallels lipogenesis but not antioxidant processes in rat liver. Am. J. Physiol. Endocrinol. Metab. 314, E543–E551 (2018).
Bianchi, G. et al. Impaired insulin-mediated amino acid plasma disappearance in non-alcoholic fatty liver disease: a feature of insulin resistance. Dig. Liver Dis. 35, 722–727 (2003).
Mardinoglu, A. et al. Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease. Nat. Commun. 5, 3083 (2014).
Zhou, Y. et al. Noninvasive detection of nonalcoholic steatohepatitis using clinical markers and circulating levels of lipids and metabolites. Clin. Gastroenterol. Hepatol. 14, 1463–1472 (2016).
Rom, O. et al. Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.aaz2841 (2020).
Sim, W. C. et al. Downregulation of PHGDH expression and hepatic serine level contribute to the development of fatty liver disease. Metabolism 102, 154000 (2020).
Mardinoglu, A. et al. Personal model-assisted identification of NAD+ and glutathione metabolism as intervention target in NAFLD. Mol. Syst. Biol. 13, 916 (2017).
Gaggini, M. et al. Altered amino acid concentrations in NAFLD: impact of obesity and insulin resistance. Hepatology 67, 145–158 (2018).
Sim, W. C. et al. l-serine supplementation attenuates alcoholic fatty liver by enhancing homocysteine metabolism in mice and rats. J. Nutr. 145, 260–267 (2015).
Chen, H. et al. Renal UTX–PHGDH–serine axis regulates metabolic disorders in the kidney and liver. Nat. Commun. 13, 3835 (2022).
Handzlik, M. K. et al. Insulin-regulated serine and lipid metabolism drive peripheral neuropathy. Nature 614, 118–124 (2023).
Zeybel, M. et al. Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients. Mol. Syst. Biol. 17, e10459 (2021).
Zhang, C. et al. The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease. Mol. Syst. Biol. 16, e9495 (2020).
Kurniawan, H., Kobayashi, T. & Brenner, D. The emerging role of one-carbon metabolism in T cells. Curr. Opin. Biotechnol. 68, 193–201 (2021).
This work was financially supported by Knut and Alice Wallenberg Foundation (grant no. 72110).
A.M., J.B. and M.U. are the founders and shareholders of ScandiBio Therapeutics, and they filed a patent application (US11141396B2) on the use of combined metabolic activators including serine to treat NAFLD patients. The other authors declare no competing interests.
Peer review information
Nature Metabolism thanks Rotonya M. Carr and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Yang, H., Zhang, C., Turkez, H. et al. Revisiting the role of serine metabolism in hepatic lipogenesis. Nat Metab 5, 760–761 (2023). https://doi.org/10.1038/s42255-023-00792-0