期刊
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
卷 43, 期 -, 页码 11-17出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2017.01.012
关键词
Colonic inflammation; Colon cancer; Interleukin-6; High-calorie diet; Purple-fleshed potatoes; Pig model
资金
- USDA-NIFA NRI Integrated Grant [2009-55200-05197]
- NIFA [2009-55200-05197, 688167] Funding Source: Federal RePORTER
Studies have shown a causal link between high-calorie diet (HCD) and colon cancer. However, molecular mechanisms are not fully elucidated. To understand etiology of HCD-induced colon carcinogenesis, we screened 10 pathways linked to elevated colonic cell proliferation and chronic inflammation in an HCDconsuming human-relevant pig model. We observed elevated colonic mucosal interleukin-6 (IL-6) expression in HCD-consuming pigs compared to standard diet controls (SD, P=.04), and IL-6 strongly correlated with Ki-67 proliferative index and zone, early biomarkers of colon cancer risk (r=0.604 and 0.743 and P=.017 and .002, respectively). Liquid chromatography-tandem mass spectrometry-based proteomic analysis and Ingenuity Pathway Analysis showed that HCD consumption altered IL-6 signaling pathway proteins (PI3KR4, IL-1 alpha, Mapk10, Akt3, PIK3CG, PIK3R5, Map2k2). Furthermore, these proteins also correlated with Ki-67 proliferative index/zone. Anti-IL-6 therapeutics are available for treating colon cancer; however, they are expensive and induce negative side effects. Thus, whole foods could be a better way to combat low-grade chronic colonic inflammation and colon cancer. Whole plant foods have been shown to decrease chronic diseases due to the potential of anti-inflammatory dietary compounds acting synergistically. We observed that supplementation of HCD with anthocyanincontaining purple-fleshed potatoes (10% w/w), even after baking, suppressed HCD-induced IL-6 expression (P=.03) and the IL-6-related proteins IL-1 alpha and Map2k1 (P <=.1). Our results highlight the importance of IL-6 signaling in diet-linked induction/prevention of colonic inflammation/cancer and demonstrate the potential of a food-based approach to target IL-6 signaling. (C) 2017 Elsevier Inc. All rights reserved.
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