Abstract
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.
Highlights
Obesity is a major risk factor for colon cancer, as well as accelerated disease progression [1] and related mortality [2, 3]
Walnuts and Intestinal Cancer Prevention of body fat appears to be even more revealing, as surrogate measures of abdominal obesity more strongly predict colon cancer risk in both men and women [5], and we have shown that this link is causal in a mouse model [6]
A total of four pelleted diets were generated for this study: a control low-fat diet (LFD), an isocaloric LFD in which walnuts were incorporated at 6% by weight (LFD+W), a control high fat diet (HFD), and an isocaloric high-fat diet (HFD) containing 7.67% walnuts by weight (HFD+W)
Summary
Obesity is a major risk factor for colon cancer, as well as accelerated disease progression [1] and related mortality [2, 3]. While general obesity (BMI) is clearly linked to colon cancer risk, the distribution. Walnuts and Intestinal Cancer Prevention of body fat appears to be even more revealing, as surrogate measures of abdominal obesity more strongly predict colon cancer risk in both men and women [5], and we have shown that this link is causal in a mouse model [6]. It has become clear that the ramifications of obesity on intestinal homeostasis can be observed well before the onset of tumor formation, with marked effects on tissue morphology [8], function [9], and a “molecular signature” which may “prime” intestinal cells toward a more tumorigenic predisposition [10], increasing tumor incidence and progression in the presence of an oncogenic insult. Given the alarmingly high rates of obesity in the US and globally, and its clear link to cancer, it is critical to identify practical strategies that can break this link
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
