Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Revisiting the role of serine metabolism in hepatic lipogenesis

Matters Arising to this article was published on 11 May 2023

The Original Article was published on 29 November 2021

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout


  1. Zhang, Z. et al. Serine catabolism generates liver NADPH and supports hepatic lipogenesis. Nat. Metab. 3, 1608–1620 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 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).

    Article  CAS  PubMed  Google Scholar 

  4. 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).

    Article  PubMed  Google Scholar 

  5. 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).

    Article  CAS  PubMed  Google Scholar 

  6. Rom, O. et al. Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome. Sci. Transl. Med. (2020).

  7. 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).

  8. Mardinoglu, A. et al. Personal model-assisted identification of NAD+ and glutathione metabolism as intervention target in NAFLD. Mol. Syst. Biol. 13, 916 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gaggini, M. et al. Altered amino acid concentrations in NAFLD: impact of obesity and insulin resistance. Hepatology 67, 145–158 (2018).

    Article  CAS  PubMed  Google Scholar 

  10. 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).

    Article  PubMed  Google Scholar 

  11. Chen, H. et al. Renal UTX–PHGDH–serine axis regulates metabolic disorders in the kidney and liver. Nat. Commun. 13, 3835 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Handzlik, M. K. et al. Insulin-regulated serine and lipid metabolism drive peripheral neuropathy. Nature 614, 118–124 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zeybel, M. et al. Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients. Mol. Syst. Biol. 17, e10459 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kurniawan, H., Kobayashi, T. & Brenner, D. The emerging role of one-carbon metabolism in T cells. Curr. Opin. Biotechnol. 68, 193–201 (2021).

    Article  CAS  PubMed  Google Scholar 

Download references


This work was financially supported by Knut and Alice Wallenberg Foundation (grant no. 72110).

Author information

Authors and Affiliations



H.Y. and A.M. drafted the manuscript. C.Z., H.T., M.U. and J.B. contributed to the writing of the manuscript.

Corresponding author

Correspondence to Adil Mardinoglu.

Ethics declarations

Competing interests

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

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.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research