title: Mechanisms linking obesity to altered metabolism in mice colon carcinogenesis.
abstract: 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.
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Lili
authors.initials: L
authors.lastname: Nimri
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Janan
authors.initials: J
authors.lastname: Saadi
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Irena
authors.initials: I
authors.lastname: Peri
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Einav
authors.initials: E
authors.lastname: Yehuda-Shnaidman
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Betty
authors.initials: B
authors.lastname: Schwartz
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D002450:Cell Communication; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017077:Culture Media, Conditioned / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004734:Energy Metabolism; D015972:Gene Expression Regulation, Neoplastic; D018836:Inflammation Mediators / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D010101:Oxygen Consumption; D019899:Paracrine Communication; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D050151:Subcutaneous Fat / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques; D047368:Tumor Burden
chemical_list: D017077:Culture Media, Conditioned; D018836:Inflammation Mediators; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases
keywords: JNK/STAT3; colon cancer; leptin; mitochondria; obesity