Cargando…

Modulation of inter-organ signalling in obese mice by spontaneous physical activity during mammary cancer development

Accumulative evidence links breast cancer development to excess weight and obesity. During obesity, dysregulations of adipose tissue induce an increase in pro-inflammatory adipokine secretions, such as leptin and oestrogen secretions. Furthermore, a raise in oxidative stress, along with a decrease i...

Descripción completa

Detalles Bibliográficos
Autores principales: Le Guennec, Delphine, Hatte, Victor, Farges, Marie-Chantal, Rougé, Stéphanie, Goepp, Marie, Caldefie-Chezet, Florence, Vasson, Marie- Paule, Rossary, Adrien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260359/
https://www.ncbi.nlm.nih.gov/pubmed/32472095
http://dx.doi.org/10.1038/s41598-020-65131-9
_version_ 1783540293228822528
author Le Guennec, Delphine
Hatte, Victor
Farges, Marie-Chantal
Rougé, Stéphanie
Goepp, Marie
Caldefie-Chezet, Florence
Vasson, Marie- Paule
Rossary, Adrien
author_facet Le Guennec, Delphine
Hatte, Victor
Farges, Marie-Chantal
Rougé, Stéphanie
Goepp, Marie
Caldefie-Chezet, Florence
Vasson, Marie- Paule
Rossary, Adrien
author_sort Le Guennec, Delphine
collection PubMed
description Accumulative evidence links breast cancer development to excess weight and obesity. During obesity, dysregulations of adipose tissue induce an increase in pro-inflammatory adipokine secretions, such as leptin and oestrogen secretions. Furthermore, a raise in oxidative stress, along with a decrease in antioxidant capacity, induces and maintains chronic inflammation, which creates a permissive environment for cancer development. Physical activity is recommended as a non-pharmacological therapy in both obese and cancer situations. Physical activity is associated with a moderation of acute inflammation, higher antioxidant defences and adipokine regulation, linked to a decrease of tumour-cell proliferation. However, the biological mechanisms underlying the relationship between oxidative stress, low-grade inflammation, carcinogenesis, obesity and physical activity are poorly understood. Our study is based on old, ovariectomised mice (C57BL/6J mice, 33 weeks old), fed with a high fat diet which increases adipose tissue favouring overweight and obesity, and housed in either an enriched environment, promoting physical activity and social interactions, or a standard environment constituting close to sedentary conditions. Our model of mammary carcinogenesis allowed for the exploration of tissue secretions and signalling pathway activation as well as the oxidative status in tumours to clarify the mechanisms involved in a multiple factorial analysis of the data set. The multiple factorial analysis demonstrated that the most important variables linked to moderate, spontaneous physical activity were the increase in growth factor (epithelial growth factor (EGF), hepatocyte growth factor (HGF)) and the activation of the signalling pathways (STAT3, c-jun n-terminal kinases (JNK), EKR1/2, nuclear factor-kappa B (NF-κB)) in the gastrocnemius (G). In inguinal adipose tissue, the NF-κB inflammation pathway was activated, increasing the IL-6 content. The adiponectin plasma (P) level increased and presented an inverse correlation with tumour oxidative status. Altogether, these results demonstrated that spontaneous physical activity in obesity conditions could slow down tumour growth through crosstalk between muscle, adipose tissue and tumour. A spontaneous moderate physical activity was able to modify the inter-organ exchange in a paracrine manner. The different tissues changed their signalling pathways and adipokine/cytokine secretions, such as adiponectin and leptin, resulting in a decrease in anti-oxidative response and inflammation in the tumour environment. This model showed that moderate, spontaneous physical activity suppresses tumour growth via a dialogue between the organs close to the tumour.
format Online
Article
Text
id pubmed-7260359
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-72603592020-06-05 Modulation of inter-organ signalling in obese mice by spontaneous physical activity during mammary cancer development Le Guennec, Delphine Hatte, Victor Farges, Marie-Chantal Rougé, Stéphanie Goepp, Marie Caldefie-Chezet, Florence Vasson, Marie- Paule Rossary, Adrien Sci Rep Article Accumulative evidence links breast cancer development to excess weight and obesity. During obesity, dysregulations of adipose tissue induce an increase in pro-inflammatory adipokine secretions, such as leptin and oestrogen secretions. Furthermore, a raise in oxidative stress, along with a decrease in antioxidant capacity, induces and maintains chronic inflammation, which creates a permissive environment for cancer development. Physical activity is recommended as a non-pharmacological therapy in both obese and cancer situations. Physical activity is associated with a moderation of acute inflammation, higher antioxidant defences and adipokine regulation, linked to a decrease of tumour-cell proliferation. However, the biological mechanisms underlying the relationship between oxidative stress, low-grade inflammation, carcinogenesis, obesity and physical activity are poorly understood. Our study is based on old, ovariectomised mice (C57BL/6J mice, 33 weeks old), fed with a high fat diet which increases adipose tissue favouring overweight and obesity, and housed in either an enriched environment, promoting physical activity and social interactions, or a standard environment constituting close to sedentary conditions. Our model of mammary carcinogenesis allowed for the exploration of tissue secretions and signalling pathway activation as well as the oxidative status in tumours to clarify the mechanisms involved in a multiple factorial analysis of the data set. The multiple factorial analysis demonstrated that the most important variables linked to moderate, spontaneous physical activity were the increase in growth factor (epithelial growth factor (EGF), hepatocyte growth factor (HGF)) and the activation of the signalling pathways (STAT3, c-jun n-terminal kinases (JNK), EKR1/2, nuclear factor-kappa B (NF-κB)) in the gastrocnemius (G). In inguinal adipose tissue, the NF-κB inflammation pathway was activated, increasing the IL-6 content. The adiponectin plasma (P) level increased and presented an inverse correlation with tumour oxidative status. Altogether, these results demonstrated that spontaneous physical activity in obesity conditions could slow down tumour growth through crosstalk between muscle, adipose tissue and tumour. A spontaneous moderate physical activity was able to modify the inter-organ exchange in a paracrine manner. The different tissues changed their signalling pathways and adipokine/cytokine secretions, such as adiponectin and leptin, resulting in a decrease in anti-oxidative response and inflammation in the tumour environment. This model showed that moderate, spontaneous physical activity suppresses tumour growth via a dialogue between the organs close to the tumour. Nature Publishing Group UK 2020-05-29 /pmc/articles/PMC7260359/ /pubmed/32472095 http://dx.doi.org/10.1038/s41598-020-65131-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Le Guennec, Delphine
Hatte, Victor
Farges, Marie-Chantal
Rougé, Stéphanie
Goepp, Marie
Caldefie-Chezet, Florence
Vasson, Marie- Paule
Rossary, Adrien
Modulation of inter-organ signalling in obese mice by spontaneous physical activity during mammary cancer development
title Modulation of inter-organ signalling in obese mice by spontaneous physical activity during mammary cancer development
title_full Modulation of inter-organ signalling in obese mice by spontaneous physical activity during mammary cancer development
title_fullStr Modulation of inter-organ signalling in obese mice by spontaneous physical activity during mammary cancer development
title_full_unstemmed Modulation of inter-organ signalling in obese mice by spontaneous physical activity during mammary cancer development
title_short Modulation of inter-organ signalling in obese mice by spontaneous physical activity during mammary cancer development
title_sort modulation of inter-organ signalling in obese mice by spontaneous physical activity during mammary cancer development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260359/
https://www.ncbi.nlm.nih.gov/pubmed/32472095
http://dx.doi.org/10.1038/s41598-020-65131-9
work_keys_str_mv AT leguennecdelphine modulationofinterorgansignallinginobesemicebyspontaneousphysicalactivityduringmammarycancerdevelopment
AT hattevictor modulationofinterorgansignallinginobesemicebyspontaneousphysicalactivityduringmammarycancerdevelopment
AT fargesmariechantal modulationofinterorgansignallinginobesemicebyspontaneousphysicalactivityduringmammarycancerdevelopment
AT rougestephanie modulationofinterorgansignallinginobesemicebyspontaneousphysicalactivityduringmammarycancerdevelopment
AT goeppmarie modulationofinterorgansignallinginobesemicebyspontaneousphysicalactivityduringmammarycancerdevelopment
AT caldefiechezetflorence modulationofinterorgansignallinginobesemicebyspontaneousphysicalactivityduringmammarycancerdevelopment
AT vassonmariepaule modulationofinterorgansignallinginobesemicebyspontaneousphysicalactivityduringmammarycancerdevelopment
AT rossaryadrien modulationofinterorgansignallinginobesemicebyspontaneousphysicalactivityduringmammarycancerdevelopment