Effects of obesity and exercise on colon cancer induction and hematopoiesis in mice

Russell Emmons, Guanying Xu, Diego Hernández-Saavedra, Adam Kriska, Yuan Xiang Pan, Hong Chen, Michael De Lisio

Research output: Contribution to journalArticle

Abstract

Obesity-induced inflammation is associated with increased risk for colorectal cancer (CRC). The role of diet and exercise in modulating increased CRC risk in obesity and the potential role of altered hematopoiesis as a contributor to these effects remain unknown. The purpose of this study was to examine how weight loss induced during CRC induction with or without exercise alters CRC initiation and its relationship to altered hematopoiesis. Mice consumed either a control (CON) or a high-fat diet to induce obesity. All mice were then placed on the control diet during CRC induction with azoxymethane (AOM). Following AOM injection, mice originally on the high-fat diet were randomized into sedentary (HF-SED) or exercise trained (HF-EX) conditions. At euthanasia, body weight and fat mass were similar among all three groups (P < 0.05). Compared with CON and HF-EX, HF-SED developed increased content of preneoplastic lesions (P < 0.05), and HF-SED had significantly increased markers of colon inflammation compared with CON. Compared with both CON and HF-EX, HF-SED had decreased content of short-term hematopoietic stem cells and increased content of common myeloid progenitor cells (both P < 0.05). Similarly, HF-SED had increased bone marrow adiposity compared with CON and HF-EX (P < 0.05), and proteomics analysis revealed an increased marker of bone marrow inflammation in HF-SED compared with CON and HF-EX. Our results suggest that the early removal of a high-fat diet reduces CRC incidence when combined with an exercise training intervention. This reduction in risk was related to lower colon inflammation with anti-inflammatory changes in hematopoiesis induced by exercise.

Original languageEnglish (US)
Pages (from-to)E210-E220
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume316
Issue number2
DOIs
StatePublished - Feb 1 2019

Keywords

  • Aberrant crypt foci
  • Hematopoietic stem/progenitor cell
  • Marrow adipose tissue inflammation
  • Mesenchymal stem/stromal cell

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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