Mediterranean diet improves liver health but does not protect against azoxymethane-induced colon tumorigenesis compared to Western diet in A/J mice

Introduction: Abundant evidence indicates that the Mediterranean (MED) diet pattern is beneficial for health, especially cardiovascular health. Epidemiological evidence indicates that the MED diet also affords protection against colorectal cancer (CRC). To date, preclinical models have only evaluate...

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Main Authors: Weimin Guo, Nicholas Crossland, Jimmy W. Crott
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Experimental and Molecular Pathology
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Online Access:http://www.sciencedirect.com/science/article/pii/S0014480025000024
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author Weimin Guo
Nicholas Crossland
Jimmy W. Crott
author_facet Weimin Guo
Nicholas Crossland
Jimmy W. Crott
author_sort Weimin Guo
collection DOAJ
description Introduction: Abundant evidence indicates that the Mediterranean (MED) diet pattern is beneficial for health, especially cardiovascular health. Epidemiological evidence indicates that the MED diet also affords protection against colorectal cancer (CRC). To date, preclinical models have only evaluated specific MED diet components and therefore, although supportive, fall short of confirming the chemoprotective capacity of this complex dietary pattern. We sought to address this gap. Method: A/J mice were randomized to receive Western (WRN) or MED diets differing in their fat, protein, and carbohydrate sources. Azoxymethane (AOM) was used to initiate colon tumorigenesis and mice were maintained for 19 weeks after the final dose. Result: Unexpectedly high mortality was observed amongst male mice following the second AOM dose. At the end of the study hepatic Cyp2E1, an enzyme that metabolize AOM, was lower in males than females. Livers from MED diet mice were significantly lighter, had lower histologic Non-Alcoholic Fatty Liver Disease (NAFLD) scores, and contained less triglycerides than WRN mice. Amongst females, serum alanine transaminase (ALT) was also lower in MED than WRN mice. Amongst male mice, those fed MED diet presented with significantly more colonic tumors than those on the WRN diet. Conclusion: In this study male mice displayed elevated sensitivity to AOM-induced hepatotoxicity and mortality than females. In agreement with human and preclinical data, livers of MED-diet-fed mice were healthier than those fed WRN diets. We could not confirm the chemoprotective capacity of the MED diet. Additional studies are required to evaluate the purported anticancer effect of the MED diet.
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spelling doaj-art-609bd6b50f514f2a9a92af5d1acecd152025-02-08T04:59:17ZengElsevierExperimental and Molecular Pathology1096-09452025-03-01141104953Mediterranean diet improves liver health but does not protect against azoxymethane-induced colon tumorigenesis compared to Western diet in A/J miceWeimin Guo0Nicholas Crossland1Jimmy W. Crott2Department of Pathology and Laboratory Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States of AmericaDepartment of Pathology and Laboratory Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States of America; Comparative Pathology Laboratory, Boston University National Emerging Infectious Diseases Laboratories, Boston, MA, United States of America; Department of Virology, Immunology & Microbiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States of AmericaDepartment of Pathology and Laboratory Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States of America; Corresponding author.Introduction: Abundant evidence indicates that the Mediterranean (MED) diet pattern is beneficial for health, especially cardiovascular health. Epidemiological evidence indicates that the MED diet also affords protection against colorectal cancer (CRC). To date, preclinical models have only evaluated specific MED diet components and therefore, although supportive, fall short of confirming the chemoprotective capacity of this complex dietary pattern. We sought to address this gap. Method: A/J mice were randomized to receive Western (WRN) or MED diets differing in their fat, protein, and carbohydrate sources. Azoxymethane (AOM) was used to initiate colon tumorigenesis and mice were maintained for 19 weeks after the final dose. Result: Unexpectedly high mortality was observed amongst male mice following the second AOM dose. At the end of the study hepatic Cyp2E1, an enzyme that metabolize AOM, was lower in males than females. Livers from MED diet mice were significantly lighter, had lower histologic Non-Alcoholic Fatty Liver Disease (NAFLD) scores, and contained less triglycerides than WRN mice. Amongst females, serum alanine transaminase (ALT) was also lower in MED than WRN mice. Amongst male mice, those fed MED diet presented with significantly more colonic tumors than those on the WRN diet. Conclusion: In this study male mice displayed elevated sensitivity to AOM-induced hepatotoxicity and mortality than females. In agreement with human and preclinical data, livers of MED-diet-fed mice were healthier than those fed WRN diets. We could not confirm the chemoprotective capacity of the MED diet. Additional studies are required to evaluate the purported anticancer effect of the MED diet.http://www.sciencedirect.com/science/article/pii/S0014480025000024AzoxymethaneMediterranean dietColorectal cancerNon-alcoholic fatty liver disease (NAFLD)
spellingShingle Weimin Guo
Nicholas Crossland
Jimmy W. Crott
Mediterranean diet improves liver health but does not protect against azoxymethane-induced colon tumorigenesis compared to Western diet in A/J mice
Experimental and Molecular Pathology
Azoxymethane
Mediterranean diet
Colorectal cancer
Non-alcoholic fatty liver disease (NAFLD)
title Mediterranean diet improves liver health but does not protect against azoxymethane-induced colon tumorigenesis compared to Western diet in A/J mice
title_full Mediterranean diet improves liver health but does not protect against azoxymethane-induced colon tumorigenesis compared to Western diet in A/J mice
title_fullStr Mediterranean diet improves liver health but does not protect against azoxymethane-induced colon tumorigenesis compared to Western diet in A/J mice
title_full_unstemmed Mediterranean diet improves liver health but does not protect against azoxymethane-induced colon tumorigenesis compared to Western diet in A/J mice
title_short Mediterranean diet improves liver health but does not protect against azoxymethane-induced colon tumorigenesis compared to Western diet in A/J mice
title_sort mediterranean diet improves liver health but does not protect against azoxymethane induced colon tumorigenesis compared to western diet in a j mice
topic Azoxymethane
Mediterranean diet
Colorectal cancer
Non-alcoholic fatty liver disease (NAFLD)
url http://www.sciencedirect.com/science/article/pii/S0014480025000024
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