High-Fat Diet-Induced Complement Activation Mediates Intestinal Inflammation and Neoplasia, Independent of Obesity. Academic Article uri icon

Overview

abstract

  • UNLABELLED: Obesity and related metabolic disturbances are closely associated with pathologies that represent a significant burden to global health. Epidemiological and molecular evidence links obesity and metabolic status with inflammation and increased risk of cancer. Here, using a mouse model of intestinal neoplasia and strains that are susceptible or resistant to diet-induced obesity, it is demonstrated 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. IMPLICATIONS: This study characterizes the relations between diet and metabolic conditions on risk for a common cancer and identifies complement activation as a novel target for cancer prevention. Mol Cancer Res; 14(10); 953-65. ©2016 AACR.

publication date

  • August 17, 2016

Research

keywords

  • Complement C5a
  • Cytokines
  • Diet, High-Fat
  • Intestinal Neoplasms
  • Obesity

Identity

PubMed Central ID

  • PMC5330314

Scopus Document Identifier

  • 84991735313

Digital Object Identifier (DOI)

  • 10.1158/1541-7786.MCR-16-0153

PubMed ID

  • 27535705

Additional Document Info

volume

  • 14

issue

  • 10