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MECHANISMS OF DISEASE

AMPK against NASH

Nature Reviews Molecular Cell Biology volume 21, page 181 (2020)Cite this article

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Non-alcoholic steatohepatitis (NASH) is the most severe form of non-alcoholic fatty liver disease (NAFLD), which is tightly linked to overnutrition and obesity. Hepatic cell death, including apoptosis, is an important driver of NASH pathology. Saltiel and colleagues now show that NASH-associated hepatocyte apoptosis is inhibited by AMPK — a major sensor of cellular energy status.

Apoptosis is driven by the caspase cascade, which involves a series of protein cleavage and activation steps. Cleavage of pro-caspase 6 to its mature form and subsequent caspase 6 activation were elevated in LAKO mice on NASH-inducing diets. Depletion or inhibition of caspase 6 counteracted NASH-associated liver pathology in these mice. Caspase 6 activity was also increased in other mice models of NASH and in liver samples from patients with NASH, indicating a key role of caspase 6 in hepatocyte apoptosis in NASH.

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References

Original article

  • Zhao, P. et al. An AMPK–caspase-6 axis controls liver damage in nonalcoholic steatohepatitis. Science 367, 652–660 (2020)

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Related article

  • Herzig, S. & Shaw, R. J. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat. Rev. Mol. Cell Biol. 19, 121–135 (2018)

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  1. Nature Reviews Molecular Cell Biology http://www.nature.com/nrm/

    Paulina Strzyz

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  1. Paulina Strzyz
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Correspondence to Paulina Strzyz.

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Strzyz, P. AMPK against NASH. Nat Rev Mol Cell Biol 21, 181 (2020). https://doi.org/10.1038/s41580-020-0225-0

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