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Reply to: revisiting the role of serine metabolism in hepatic lipogenesis

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The Original Article was published on 11 May 2023

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Fig. 1: De novo lipogenesis flux in hepatic G6PD-knockout model (control = G6PDfl/fl; hepatic ∆G6PD = Alb-Cre+ G6PDfl/fl).

Data availability

Raw data/Source data are provided with this paper.

Code availability

El-MAVEN v.12 and natural abundance correction software AccuCor are available online on GitHub (https://github.com/ElucidataInc/ElMaven/ and https://github.com/XiaoyangSu/AccuCor/).

References

  1. Ducker, G. S. et al. Human SHMT inhibitors reveal defective glycine import as a targetable metabolic vulnerability of diffuse large B cell lymphoma. Proc. Natl Acad. Sci. USA 114, 11404–11409 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ducker, G. S. & Rabinowitz, J. D. One-carbon metabolism in health and disease. Cell Metab. 25, 27–42 (2017).

    Article  CAS  PubMed  Google Scholar 

  3. 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 

  4. Wise, E. M. & Ball, E. G. Malic enzyme and lipogenesis. Proc. Natl Acad. Sci. USA 52, 1255–1263 (1964).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Frenkel, R. Regulation and physiological functions of malic enzymes. Curr. Top. Cell Regul. 9, 157–181 (1975).

    Article  CAS  PubMed  Google Scholar 

  6. Shechter, I., Dai, P., Huo, L. & Guan, G. IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells: evidence that IDH1 may regulate lipogenesis in hepatic cells. J. Lipid Res. 44, 2169–2180 (2003).

    Article  CAS  PubMed  Google Scholar 

  7. Koh, H. J. et al. Cytosolic NADP+-dependent isocitrate dehydrogenase plays a key role in lipid metabolism. J. Biol. Chem. 279, 39968–39974 (2004).

    Article  CAS  PubMed  Google Scholar 

  8. Karlsson M, et al. A single-cell type transcriptomics map of human tissues. Sci Adv. https://doi.org/10.1126/sciadv.abh2169 (2021).

  9. 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 

  10. Zhou, X. et al. Serine prevented high-fat diet-induced oxidative stress by activating AMPK and epigenetically modulating the expression of glutathione synthesis-related genes. Biochim Biophys. Acta Mol. Basis Dis. 1864, 488–498 (2018).

    Article  CAS  PubMed  Google Scholar 

  11. 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 

  12. 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 

  13. Bates, J. et al. Acetyl-CoA carboxylase inhibition disrupts metabolic reprogramming during hepatic stellate cell activation. J. Hepatol. 73, 896–905 (2020).

    Article  CAS  PubMed  Google Scholar 

  14. Goedeke, L. et al. Acetyl-CoA carboxylase inhibition reverses NAFLD and hepatic insulin resistance but promotes hypertriglyceridemia in rodents. Hepatology 68, 2197–2211 (2018).

    Article  CAS  PubMed  Google Scholar 

  15. 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 

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Authors and Affiliations

  1. Department of Chemistry, Princeton University, Princeton, NJ, USA

    Zhaoyue Zhang & Joshua D. Rabinowitz

  2. Laboratory of Molecular Genetics, The Rockefeller University, New York, NY, USA

    Zhaoyue Zhang

  3. Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA

    Tara TeSlaa & Joshua D. Rabinowitz

  4. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA

    Tara TeSlaa

  5. Ludwig Institute for Cancer Research, Princeton Branch, Princeton, NJ, USA

    Joshua D. Rabinowitz

Authors
  1. Zhaoyue Zhang
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  2. Tara TeSlaa
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  3. Joshua D. Rabinowitz
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Contributions

Z.Z., T.T. and J.R. wrote the manuscript. This work was funded by the Allen Foundation and by Ludwig Cancer Research.

Corresponding author

Correspondence to Joshua D. Rabinowitz.

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Competing interests

J.R. is a consultant and received research funding from Pfizer and is an adviser and stock owner in Colorado Research Partners, L.E.A.F. Pharmaceuticals, Rafael Pharmaceuticals, Barer Institute and its subsidiaries, Serien Therapeutics, Empress Therapeutics, and Agios Pharmaceuticals. J.R. is co-inventor of SHIN2 and related SHMT inhibitors, which have been patented by Princeton University. The remaining authors declare no competing interests.

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Nature Metabolism thanks the anonymous reviewers for their contribution to the peer review of this work.

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Zhang, Z., TeSlaa, T. & Rabinowitz, J.D. Reply to: revisiting the role of serine metabolism in hepatic lipogenesis. Nat Metab 5, 762–764 (2023). https://doi.org/10.1038/s42255-023-00793-z

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