High-fat diet-induced complement activation mediates intestinal inflammation and neoplasia, independent of obesity

    • Using a mouse model of intestinal neoplasia and strains that are susceptible or resistant to diet-induced obesity, this study demonstrates that high-fat diet-induced inflammation, rather than obesity or metabolic status, is associated with increased intestinal neoplasia.
    • The complement fragment C5a acts as the trigger for inflammation and intestinal tumorigenesis.
    • High-fat diet induces complement activation and generation of C5a, which in turn induces the production of proinflammatory cytokines and expression of proto-oncogenes.
    • Pharmacological and genetic targeting of the C5a receptor reduced both inflammation and intestinal polyposis, suggesting the use of complement inhibitors for preventing diet-induced neoplasia.
Author and source information

Authors: Doerner SK, Reis ES, Leung ES, Ko JS, Heaney JD, Berger NA, Lambris JD, Nadeau JH.
Reference: Mol Cancer Res. 2016 Oct;14(10):953-965. Epub 2016 Aug 17.
Source: www.ncbi.nlm.nih.gov