Mechanisms linking obesity to altered metabolism in mice colon carcinogenesis
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Lili Nimri1, Janan Saadi1, Irena Peri1, Einav Yehuda-Shnaidman1, Betty Schwartz1
1Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Jerusalem, Israel
Betty Schwartz, e-mail: firstname.lastname@example.org
Keywords: obesity, colon cancer, leptin, mitochondria, JNK/STAT3
Received: August 05, 2015 Accepted: September 29, 2015 Published: October 12, 2015
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.
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