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METABOLIC DISEASES

Gutting out Myc to decrease ceramides

Nature Metabolism volume 3, pages 890–891 (2021)Cite this article

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MYC is a transcription factor controlling growth and nutrient metabolism. Luo et al. now link intestinal expression of MYC to impairments in glucose, lipid and body-weight homeostasis by uncovering novel roles of MYC in regulating the glucagon-like peptide GLP1 and the ceramide-biosynthesis regulator CERS4. Myc deletion in the intestinal epithelium prevents or reverses diet-induced obesity and hepatic steatosis in mice. Critically, people with obesity display elevated MYC and CERS4 expression in the ileum, thus further supporting the clinical relevance of these findings.

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Fig. 1: By regulating CerS4 transcription, intestinal MYC controls a gut–liver ceramide axis that regulates hepatic health, body weight and glucose homeostasis.

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Acknowledgements

The authors received research support from the US National Institutes of Health (DK115824, DK116888 and DK116450 to S.A.S.; DK112826 to W.L.H.), the Juvenile Diabetes Research Foundation (JDRF 3-SRA-2019-768-A-B to S.A.S.), the American Diabetes Association (to S.A.S.), the American Heart Association (to S.A.S.) and the Margolis Foundation (to S.A.S.).

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Authors and Affiliations

  1. Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, USA

    Ying Li, Scott A. Summers & William L. Holland

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  1. Ying Li
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  2. Scott A. Summers
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  3. William L. Holland
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Correspondence to William L. Holland.

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Competing interests

S.A.S. is a consultant, co-founder and shareholder of Centaurus Therapeutics. The other authors declare no competing interests.

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Li, Y., Summers, S.A. & Holland, W.L. Gutting out Myc to decrease ceramides. Nat Metab 3, 890–891 (2021). https://doi.org/10.1038/s42255-021-00418-3

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