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Volume 36, Issue 12, Pages 1325-1334 (December 2016)
High-fat Western diet–induced obesity contributes to increased tumor growth in mouse models of human colon cancer Ann Marie O'Neill, Christine M. Burrington, Erin A. Gillaspie, Darin T. Lynch, Melissa J. Horsman, Michael W. Greene Nutrition Research Volume 36, Issue 12, Pages (December 2016) DOI: /j.nutres Copyright © 2016 Elsevier Inc. Terms and Conditions
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Fig. 1 Mice fed HFWD become obese, with increasingly impaired glucose tolerance and increased insulin resistance. a, Means ± SE of body weights obtained from mice fed either LFWD or HFWD at 4, 8, and 12 weeks show increased weight gain over time in HFWD animals. Means ± SE of normalized liver (b) and EWAT weights (c) obtained from HFWD- and LFWD-fed mice after 12 weeks. To investigate the effects of each of the diets on insulin resistance and glucose metabolism, ITTs and GTTs were performed on both groups after 4, 8, and 12 weeks on the respective diets and the area under the curve was determined. d, The percent reduction in the mean glucose concentration in ITT curves at 4, 8, and 12 weeks is shown as the means ± SE. e, GTT results of both LFWD and HFWD at 4, 8, and 12 weeks. f, Means ± SE of the area under the curve calculated for each GTT curve. * P < .05; *** P < .001. Nutrition Research , DOI: ( /j.nutres ) Copyright © 2016 Elsevier Inc. Terms and Conditions
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Fig. 2 Subcutaneous human colon cancer tumor growth. a, Subcutaneous HT-29 tumors in obese mice fed an HFWD (n = 13) shown accelerated and increased tumor growth over 4 weeks compared with mice fed an LFWD (n = 14). Shown are the means ± SE of the estimated tumor weight. b, Representative tumors from each group. c, Subcutaneous HCT-116 tumors in normal-weight mice fed an HFWD (n = 14) diet do not differ in size from tumors in mice fed an LFWD (n = 11). Shown are the means ± SE of the estimated tumor weight. d, Representative tumors from each group are shown. e, Spearman correlation of body weight and serum parameters with tumor growth. Shown is the correlation coefficient. Insulin is associated with a decreased tumor size in LFWD mice but conversely with an increased tumor size in HFWD mice. * P < .05; *** P < .001; ns, not significant. Nutrition Research , DOI: ( /j.nutres ) Copyright © 2016 Elsevier Inc. Terms and Conditions
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Fig. 3 Increased tumor growth and differential protein activation and gene expression in an orthotopic model of human colon cancer in mice fed an HFWD. a, Final tumor weight of orthotopic tumors from mice fed either an LFWD (n = 10) or an HFWD (n = 8) is shown as box plots. The top and bottom of the boxes define the 25th and 75th percentiles. The middle line is the median class score. The error bars define the 10th and 90th percentiles. The dots are outliers (scores that fell outside the 10th and 90th percentiles). Representative orthotopic tumors from both lean and obese mice (b) and corresponding fluorescent image (c). d, Correlation analysis was performed using the Spearman correlation coefficient test. Shown is the correlation coefficient. In mice fed an LFWD, normalized EWAT size and leptin levels correlated inversely with tumor size. In the HFWD, serum leptin levels also negatively correlated with tumor size. e, JNK phosphorylation in tumors from mice fed an HFWD (n = 8) and LFWD (n = 10) is shown as a box plot as described in panel A. f, EWAT from tumor-bearing mice fed an HFWD (n = 8) showed increased expression of MCP1 by 4.9-fold, compared with LFWD (n = 10). Shown are the means ± SE. g, Total protein expressions of caspase 3, caspase 7, and PARP in tumors from mice fed an HFWD (n = 8) and LFWD (n = 10) are shown as representative Western blots (upper panel) and the means ± SE (lower panel). * P < .05; ** P < .01; *** P < .001. Nutrition Research , DOI: ( /j.nutres ) Copyright © 2016 Elsevier Inc. Terms and Conditions
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