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Mechanisms linking obesity to altered metabolism in mice colon carcinogenesis
There are an increasing number of reports on obesity being a key risk factor for the development of colon cancer. Our goal in this study was to explore the metabolic networks and molecular signaling pathways linking obesity, adipose tissue and colon cancer. Using in-vivo experiments, we found that m...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741993/ https://www.ncbi.nlm.nih.gov/pubmed/26472027 |
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author | Nimri, Lili Saadi, Janan Peri, Irena Yehuda-Shnaidman, Einav Schwartz, Betty |
author_facet | Nimri, Lili Saadi, Janan Peri, Irena Yehuda-Shnaidman, Einav Schwartz, Betty |
author_sort | Nimri, Lili |
collection | PubMed |
description | There are an increasing number of reports on obesity being a key risk factor for the development of colon cancer. Our goal in this study was to explore the metabolic networks and molecular signaling pathways linking obesity, adipose tissue and colon cancer. Using in-vivo experiments, we found that mice fed a high-fat diet (HFD) and injected with MC38 colon cancer cells develop significantly larger tumors than their counterparts fed a control diet. In ex-vivo experiments, MC38 and CT26 colon cancer cells exposed to conditioned media (CM) from the adipose tissue of HFD-fed mice demonstrated significantly lower oxygen consumption rate as well as lower maximal oxygen consumption rate after carbonyl cyanide-4-trifluoromethoxy-phenylhydrazone treatment. In addition, in-vitro assays showed downregulated expression of mitochondrial genes in colon cancer cells exposed to CM prepared from the visceral fat of HFD-fed mice or to leptin. Interestingly, leptin levels detected in the media of adipose tissue explants co-cultured with MC38 cancer cells were higher than in adipose tissue explants cultures, indicating cross talk between the adipose tissue and the cancer cells. Salient findings of the present study demonstrate that this crosstalk is mediated at least partially by the JNK/STAT3-signaling pathway. |
format | Online Article Text |
id | pubmed-4741993 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-47419932016-03-17 Mechanisms linking obesity to altered metabolism in mice colon carcinogenesis Nimri, Lili Saadi, Janan Peri, Irena Yehuda-Shnaidman, Einav Schwartz, Betty Oncotarget Research Paper There are an increasing number of reports on obesity being a key risk factor for the development of colon cancer. Our goal in this study was to explore the metabolic networks and molecular signaling pathways linking obesity, adipose tissue and colon cancer. Using in-vivo experiments, we found that mice fed a high-fat diet (HFD) and injected with MC38 colon cancer cells develop significantly larger tumors than their counterparts fed a control diet. In ex-vivo experiments, MC38 and CT26 colon cancer cells exposed to conditioned media (CM) from the adipose tissue of HFD-fed mice demonstrated significantly lower oxygen consumption rate as well as lower maximal oxygen consumption rate after carbonyl cyanide-4-trifluoromethoxy-phenylhydrazone treatment. In addition, in-vitro assays showed downregulated expression of mitochondrial genes in colon cancer cells exposed to CM prepared from the visceral fat of HFD-fed mice or to leptin. Interestingly, leptin levels detected in the media of adipose tissue explants co-cultured with MC38 cancer cells were higher than in adipose tissue explants cultures, indicating cross talk between the adipose tissue and the cancer cells. Salient findings of the present study demonstrate that this crosstalk is mediated at least partially by the JNK/STAT3-signaling pathway. Impact Journals LLC 2015-10-12 /pmc/articles/PMC4741993/ /pubmed/26472027 Text en Copyright: © 2015 Nimri et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Nimri, Lili Saadi, Janan Peri, Irena Yehuda-Shnaidman, Einav Schwartz, Betty Mechanisms linking obesity to altered metabolism in mice colon carcinogenesis |
title | Mechanisms linking obesity to altered metabolism in mice colon carcinogenesis |
title_full | Mechanisms linking obesity to altered metabolism in mice colon carcinogenesis |
title_fullStr | Mechanisms linking obesity to altered metabolism in mice colon carcinogenesis |
title_full_unstemmed | Mechanisms linking obesity to altered metabolism in mice colon carcinogenesis |
title_short | Mechanisms linking obesity to altered metabolism in mice colon carcinogenesis |
title_sort | mechanisms linking obesity to altered metabolism in mice colon carcinogenesis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741993/ https://www.ncbi.nlm.nih.gov/pubmed/26472027 |
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