TY - JOUR
T1 - Dietary Walnuts Protect Against Obesity-Driven Intestinal Stem Cell Decline and Tumorigenesis
AU - Guan, Fangxia
AU - Tabrizian, Tahmineh
AU - Novaj, Ardijana
AU - Nakanishi, Masako
AU - Rosenberg, Daniel W.
AU - Huffman, Derek M.
N1 - Funding Information:
This work was supported by the NIA (R56AG052981; R21AG055026), the American Institute for Cancer Research (AICR) and the California Walnut Commission. The authors would also like to acknowledge the NCI supported Einstein Cancer Center (P30CA013330), the Einstein Nathan Shock Center for Excellence in the Biology of Aging (P30AG038072), and the Einstein-Sinai Diabetes Research Center (P30DK20541). Experiments performed in the Einstein Analytical Imaging Core were supported by an NIH SIG award (#1S10OD019961-01). TT is supported by a T32 Training Grant (T32AG23475). The content provided in this manuscript does not necessarily represent the official views of the AICR and the California Walnut Commission and is solely the responsibility of the authors with no input on interpretation or reporting of findings by the sponsors.
Publisher Copyright:
© Copyright © 2018 Guan, Tabrizian, Novaj, Nakanishi, Rosenberg and Huffman.
PY - 2018/5/31
Y1 - 2018/5/31
N2 - Obesity can negatively impact intestinal homeostasis, and increase colon cancer risk and related mortality. Thus, given the alarmingly high rates of obesity in the US and globally, it is critical to identify practical strategies that can break the obesity-cancer link. Walnuts have been increasingly recognized to mitigate cancer risk, and contain many bioactive constituents with antioxidant and anti-inflammatory properties that could potentially counteract pathways thought to be initiators of obesity-related cancer. Therefore, the purpose of this study was to determine if walnuts could preserve intestinal homeostasis, and attenuate tumorigenesis and growth in the context of obesity and a high calorie diet. To this end, we studied effects of walnuts on these parameters under different dietary conditions in wildtype mice, two independent Apc models (Apc1638N/+ and ApcΔ14), and in MC38 colon cancer cells in vivo, respectively. Walnuts did not alter the metabolic phenotype or intestinal morphology in normal mice fed either a low-fat diet (LFD), LFD with 6% walnuts (LFD+W), high-fat diet (HFD), or HFD with 7.6% walnuts (HFD+W). However, walnuts did lead to a significant reduction in circulating CCL5 and preserved intestinal stem cell (ISC) function under HFD-fed conditions. Furthermore, walnuts reduced tumor multiplicity in Apc1638N/+ male HFD+W animals, as compared to HFD controls (3.7 ± 0.5 vs. 2.5 ± 0.3; P = 0.015), tended to reduce the number of adenocarcinomas (0.67 ± 0.16 vs. 0.29 ± 0.12; P = 0.07), and preferentially limited tumor growth in ApcΔ14 male mice (P = 0.019) fed a high-calorie western-style diet. In summary, these data demonstrate that walnuts confer significant protection against intestinal tumorigenesis and growth and preserve ISC function in the context of a high-calorie diet and obesity. Thus, these data add to the accumulating evidence connecting walnuts as a potentially effective dietary strategy to break the obesity-colon cancer link.
AB - Obesity can negatively impact intestinal homeostasis, and increase colon cancer risk and related mortality. Thus, given the alarmingly high rates of obesity in the US and globally, it is critical to identify practical strategies that can break the obesity-cancer link. Walnuts have been increasingly recognized to mitigate cancer risk, and contain many bioactive constituents with antioxidant and anti-inflammatory properties that could potentially counteract pathways thought to be initiators of obesity-related cancer. Therefore, the purpose of this study was to determine if walnuts could preserve intestinal homeostasis, and attenuate tumorigenesis and growth in the context of obesity and a high calorie diet. To this end, we studied effects of walnuts on these parameters under different dietary conditions in wildtype mice, two independent Apc models (Apc1638N/+ and ApcΔ14), and in MC38 colon cancer cells in vivo, respectively. Walnuts did not alter the metabolic phenotype or intestinal morphology in normal mice fed either a low-fat diet (LFD), LFD with 6% walnuts (LFD+W), high-fat diet (HFD), or HFD with 7.6% walnuts (HFD+W). However, walnuts did lead to a significant reduction in circulating CCL5 and preserved intestinal stem cell (ISC) function under HFD-fed conditions. Furthermore, walnuts reduced tumor multiplicity in Apc1638N/+ male HFD+W animals, as compared to HFD controls (3.7 ± 0.5 vs. 2.5 ± 0.3; P = 0.015), tended to reduce the number of adenocarcinomas (0.67 ± 0.16 vs. 0.29 ± 0.12; P = 0.07), and preferentially limited tumor growth in ApcΔ14 male mice (P = 0.019) fed a high-calorie western-style diet. In summary, these data demonstrate that walnuts confer significant protection against intestinal tumorigenesis and growth and preserve ISC function in the context of a high-calorie diet and obesity. Thus, these data add to the accumulating evidence connecting walnuts as a potentially effective dietary strategy to break the obesity-colon cancer link.
KW - colon cancer
KW - inflammation
KW - intestine
KW - obesity
KW - walnuts
UR - http://www.scopus.com/inward/record.url?scp=85061919854&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061919854&partnerID=8YFLogxK
U2 - 10.3389/fnut.2018.00037
DO - 10.3389/fnut.2018.00037
M3 - Article
AN - SCOPUS:85061919854
SN - 2296-861X
VL - 5
JO - Frontiers in Nutrition
JF - Frontiers in Nutrition
M1 - 37
ER -
