Voluntary physical activity abolishes the proliferative tumor growth microenvironment created by adipose tissue in animals fed a high fat diet

J Appl Physiol (1985). 2016 Jul 1;121(1):139-53. doi: 10.1152/japplphysiol.00862.2015. Epub 2016 May 5.


The molecular mechanisms behind the obesity-breast cancer association may be regulated via adipokine secretion by white adipose tissue. Specifically, adiponectin and leptin are altered with adiposity and exert antagonistic effects on cancer cell proliferation. We set out to determine whether altering adiposity in vivo via high fat diet (HFD) feeding changed the tumor growth supporting nature of adipose tissue and whether voluntary physical activity (PA) could ameliorate these HFD-dependent effects. We show that conditioned media (CM) created from the adipose tissue of HFD fed animals caused an increase in the proliferation of MCF7 cells compared with cells exposed to CM prepared from the adipose of lean chow diet fed counterparts. This increased proliferation was driven within the MCF7 cells by an HFD-dependent antagonism between AMP-activated protein kinase (AMPK) and protein kinase B (Akt) signaling pathways, decreasing p27 protein levels via reduced phosphorylation at T198 and downregulation of adiponectin receptor 1 (AdipoR1). PA can ameliorate these proliferative effects of HFD-CM on MCF7 cells, increasing p27(T198) by AMPK, reducing pAkt(T308), and increasing AdipoR1, resulting in cell cycle withdrawal in a manner that depends on the PA intensity. High physical activity (>3 km/day) completely abolished the effects of HFD feeding. In addition, AdipoR1 overexpression mimics the effects of exercise, abolishing the proliferative effects of the HFD-CM on MCF7 cells and further enhancing the antiproliferative effects of PA on the HFD-CM. Thus voluntary PA represents a means to counteract the proliferative effects of adipose tissue on breast cancers in obese patients.

Keywords: adipokines; breast cancer; obesity; physical activity.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adipokines / metabolism
  • Adiponectin / metabolism
  • Adipose Tissue / metabolism
  • Adipose Tissue / physiology*
  • Adiposity / physiology
  • Animals
  • Body Weight / physiology
  • Cell Proliferation / physiology*
  • Culture Media, Conditioned / metabolism
  • Diet, High-Fat / adverse effects*
  • Humans
  • Leptin / metabolism
  • MCF-7 Cells
  • Male
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Obesity / metabolism
  • Obesity / physiopathology
  • Physical Conditioning, Animal / physiology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology
  • Tumor Microenvironment / physiology*


  • Adipokines
  • Adiponectin
  • Culture Media, Conditioned
  • Leptin
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinases