Abstract Title:

Voluntary Physical Activity Abolishes the Proliferative Tumor Growth Microenvironment Created by Adipose Tissue in Animals Fed a High Fat Diet.

Abstract Source:

J Appl Physiol (1985). 2016 May 5:jap.00862.2015. Epub 2016 May 5. PMID: 27150834

Abstract Author(s):

Christopher F Theriau, Yaniv Shpilberg, Michael C Riddell, Michael K Connor

Article Affiliation:

Christopher F Theriau

Abstract:

The molecular mechanisms behind the obesity-breast cancer association may be regulated via adipokine secretion by white adipose tissue. Specifically, adiponectin (ADIPO) and leptin (LEP) 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 if voluntary physical activity (VPA) 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 to 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 AMPK and Akt signaling pathways, decreasing p27 protein levels via reduced phosphorylation at T198 and downregulation of AdiporR1. VPA 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 VPA 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 anti-proliferative effects physical activity on the HFD-CM. Thus, VPA represents a means to counteract the proliferative effects of adipose tissue on breast cancers in obese patients.

Study Type : Animal Study

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