High fat deals a low blow | Nature Chemical Biology

Access through your institution Buy or subscribe _Nature_, published online 26 June 2013; doi:10.1038/nature12347 Senescent cells, or those that are no longer dividing, produce the

senescence-associated secretory phenotype (SASP), marked by a cocktail of cytokines, chemokines and enzymes that has been linked to cancer risk in obesity. To understand the basis for this

link, Yoshimoto _et al_. studied the impact of diet on cancer in mice and found that cancer-prone mice consuming a high-fat diet, but not a normal diet, developed hepatocellular carcinoma.

The authors did find evidence of senescent cells in the liver, and mice lacking IL-1β, an upstream regulator of SASP induction, had smaller numbers and sizes of tumors compared to wild-type

mice. As intestinal microbiota have been linked to obesity, the authors then demonstrated that antibiotic treatment led to decreased populations of senescent cells and carcinoma. The authors

searched for a possible mediator of this interaction, identifying a single molecule—deoxycholic acid—as highly present in the serum metabolites of mice fed with high-fat but not a normal

diet. Decreasing deoxycholic acid concentrations blocked formation of carcinomas and senescent cells, and, reciprocally, treatment with this molecule increased cancer formation in mice on a

high-fat diet. These data led to a model where high fat consumption initiates deoxycholic acid production, which induces formation of senescent cells, with subsequent SASP inducing cancer.

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calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support Authors * Catherine Goodman View author

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blow. _Nat Chem Biol_ 9, 469 (2013). https://doi.org/10.1038/nchembio.1305 Download citation * Published: 18 July 2013 * Issue Date: August 2013 * DOI: https://doi.org/10.1038/nchembio.1305

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