Cargando…

Dietary Walnuts Protect Against Obesity-Driven Intestinal Stem Cell Decline and Tumorigenesis

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Guan, Fangxia, Tabrizian, Tahmineh, Novaj, Ardijana, Nakanishi, Masako, Rosenberg, Daniel W., Huffman, Derek M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990619/
https://www.ncbi.nlm.nih.gov/pubmed/29904634
http://dx.doi.org/10.3389/fnut.2018.00037
_version_ 1783329613525549056
author Guan, Fangxia
Tabrizian, Tahmineh
Novaj, Ardijana
Nakanishi, Masako
Rosenberg, Daniel W.
Huffman, Derek M.
author_facet Guan, Fangxia
Tabrizian, Tahmineh
Novaj, Ardijana
Nakanishi, Masako
Rosenberg, Daniel W.
Huffman, Derek M.
author_sort Guan, Fangxia
collection PubMed
description 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 (Apc(1638N/+) and Apc(Δ14)), 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 Apc(1638N/+) 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 Apc(Δ14) 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.
format Online
Article
Text
id pubmed-5990619
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-59906192018-06-14 Dietary Walnuts Protect Against Obesity-Driven Intestinal Stem Cell Decline and Tumorigenesis Guan, Fangxia Tabrizian, Tahmineh Novaj, Ardijana Nakanishi, Masako Rosenberg, Daniel W. Huffman, Derek M. Front Nutr Nutrition 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 (Apc(1638N/+) and Apc(Δ14)), 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 Apc(1638N/+) 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 Apc(Δ14) 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. Frontiers Media S.A. 2018-05-31 /pmc/articles/PMC5990619/ /pubmed/29904634 http://dx.doi.org/10.3389/fnut.2018.00037 Text en Copyright © 2018 Guan, Tabrizian, Novaj, Nakanishi, Rosenberg and Huffman. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Guan, Fangxia
Tabrizian, Tahmineh
Novaj, Ardijana
Nakanishi, Masako
Rosenberg, Daniel W.
Huffman, Derek M.
Dietary Walnuts Protect Against Obesity-Driven Intestinal Stem Cell Decline and Tumorigenesis
title Dietary Walnuts Protect Against Obesity-Driven Intestinal Stem Cell Decline and Tumorigenesis
title_full Dietary Walnuts Protect Against Obesity-Driven Intestinal Stem Cell Decline and Tumorigenesis
title_fullStr Dietary Walnuts Protect Against Obesity-Driven Intestinal Stem Cell Decline and Tumorigenesis
title_full_unstemmed Dietary Walnuts Protect Against Obesity-Driven Intestinal Stem Cell Decline and Tumorigenesis
title_short Dietary Walnuts Protect Against Obesity-Driven Intestinal Stem Cell Decline and Tumorigenesis
title_sort dietary walnuts protect against obesity-driven intestinal stem cell decline and tumorigenesis
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990619/
https://www.ncbi.nlm.nih.gov/pubmed/29904634
http://dx.doi.org/10.3389/fnut.2018.00037
work_keys_str_mv AT guanfangxia dietarywalnutsprotectagainstobesitydrivenintestinalstemcelldeclineandtumorigenesis
AT tabriziantahmineh dietarywalnutsprotectagainstobesitydrivenintestinalstemcelldeclineandtumorigenesis
AT novajardijana dietarywalnutsprotectagainstobesitydrivenintestinalstemcelldeclineandtumorigenesis
AT nakanishimasako dietarywalnutsprotectagainstobesitydrivenintestinalstemcelldeclineandtumorigenesis
AT rosenbergdanielw dietarywalnutsprotectagainstobesitydrivenintestinalstemcelldeclineandtumorigenesis
AT huffmanderekm dietarywalnutsprotectagainstobesitydrivenintestinalstemcelldeclineandtumorigenesis