Enriched environment inhibits breast cancer progression in obese models with intact leptin signaling.

Abstract:

:Obesity is becoming a global epidemic and is a risk factor for breast cancer. Environmental enrichment (EE), a model recapitulating an active lifestyle, leads to leanness, resistance to diet-induced obesity (DIO) and cancer. One mechanism is the activation of the hypothalamic-sympathoneural-adipocyte (HSA) axis. This results in the release of norepinephrine onto adipose tissue inducing a drop of leptin. This study aimed to test the effects of EE on breast cancer onset and progression while considering the effect of leptin by utilizing the transgenic MMTV-PyMT model as well as several models of varied leptin signaling. EE was highly effective at reducing weight gain, regardless of the presence of leptin. However, the effects of EE on tumor progression were dependent on leptin signaling. EE decreased leptin and reduced mammary tumor growth rate in MMTV-PyMT spontaneous and DIO transplantation models; in contrast, the absence of leptin in ob/ob mice resulted in increased tumor growth likely due to elevated norepinephrine levels. Our results suggest that the microenvironment is critical in breast tumorigenesis and that the drop in leptin is an important peripheral mediator of the EE anti-breast cancer effects, offsetting the potential pro-tumorigenic effects of norepinephrine responding to a complex environment.

journal_name

Endocr Relat Cancer

journal_title

Endocrine-related cancer

authors

Foglesong GD,Queen NJ,Huang W,Widstrom KJ,Cao L

doi

10.1530/ERC-19-0075

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

483-495

issue

5

eissn

1351-0088

issn

1479-6821

pii

ERC-19-0075.R1

journal_volume

26

pub_type

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