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.