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Obesity Promotes Marrow-Derived Myeloid Cell Accumulation While Exercise Reduces Proliferative Signaling in Colon

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Medicine and Science in Sports and Exercise
|October 1, 2024
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Summary

Exercise training (EX) reduces colon cancer initiation in obese mice by inhibiting aberrant crypt foci (ACF) formation. EX may work through pathways independent of myeloid cell accumulation, possibly involving reduced beta-catenin and STAT3 signaling.

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Area of Science:

  • Oncology
  • Immunology
  • Metabolism

Background:

  • Obesity is a known risk factor for colon cancer, potentially linked to myeloid cells.
  • Exercise training (EX) has shown promise in preventing colon cancer initiation.
  • The precise role of early myeloid cell accumulation and inflammation in obesity-driven colon carcinogenesis and the impact of EX remain unclear.

Purpose of the Study:

  • To investigate if early myeloid cell accumulation and inflammation precede high-fat diet (HFD)-induced obesity and colon carcinogenesis.
  • To determine if EX can attenuate these obesity-related effects.
  • To test the hypothesis that obesity promotes colon carcinogenesis via myeloid cell accumulation and inflammation, which EX can mitigate.

Main Methods:

  • Mice were fed a high-fat diet (HFD) or control (CON) diet for 8 weeks.
  • Mice received azoxymethane (AOM) to induce colon cancer and were randomized to exercise (EX) or sedentary (SED) conditions.
  • Myeloid cell populations, aberrant crypt foci (ACF), beta-catenin, and STAT3 protein levels were analyzed.

Main Results:

  • HFD-induced obesity led to increased aberrant crypt foci (ACF) formation, a marker of early colon carcinogenesis.
  • Exercise training (EX) significantly reduced ACF formation compared to sedentary conditions.
  • While EX did not alter colon immune cell populations, it reduced STAT3 protein levels and was associated with higher beta-catenin in HFD mice.

Conclusions:

  • Obesity promotes colon ACF formation, potentially mediated by early inflammatory myeloid cell accumulation.
  • Exercise training (EX) attenuates ACF formation but does not alter myeloid cell accumulation in the colon.
  • EX may inhibit colon carcinogenesis through mechanisms independent of myeloid cell modulation, possibly involving reduced beta-catenin and STAT3 signaling.