Weight loss following diet-induced obesity does not alter colon tumorigenesis in the AOM mouse model.
Obesity presents a significant public health concern given its association with increased cancer incidence, unfavorable prognosis, and metastasis. However, there is very little literature on the effects of weight loss, following obesity, on risk for colon cancer or liver cancer. Therefore, we sought to study whether intentional weight loss through diet manipulation was capable of mitigating colon and liver cancer in mice. We fed mice with a high-fat diet (HFD) comprised of 47% carbohydrates, 40% fat, and 13% protein for 20 wk to mimic human obesity. Subsequently, azoxymethane (AOM) was used to promote colon and liver carcinogenesis. A subset of obese mice was then switched to a low-fat diet (LFD) containing 67.5% carbohydrate, 12.2% fat, and 20% protein to promote intentional weight loss. Body weight loss and excess fat reduction did not protect mice from colon cancer progression and liver dysplastic lesion in the AOM-chemical-cancer model even though these mice had improved blood glucose and leptin levels. Intentional weight loss in AOM-treated mice actually produced histological changes that resemble dysplastic alterations in the liver and presented a higher percentage of F4/80+CD206+macrophages and activated T cells (CD4+CD69+) in the spleen and lymph nodes, respectively. In addition, the liver of AOM-treated mice exposed to a HFD during the entire period of the experiment exhibited a marked increase in proliferation and pNF-κB activation. Altogether, these data suggest that intentional weight loss following chemical-induced carcinogenesis does not affect colon tumorigenesis but may in fact negatively impact liver repair mechanisms.
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
Kandy T
KT
Velázquez
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
Reilly T
RT
Enos
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
Meredith S
MS
Carson
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
Taryn L
TL
Cranford
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
Jackie E
JE
Bader
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
Ioulia
I
Chatzistamou
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
Udai P
UP
Singh
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
Prakash S
PS
Nagarkatti
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
Mitzi
M
Nagarkatti
Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina.
J Mark
JM
Davis
Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina.
James A
JA
Carson
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and angela.murphy@uscmed.sc.edu.
E Angela
EA
Murphy
D000818:Animals; D001397:Azoxymethane; D001835:Body Weight; D063646:Carcinogenesis / Q000139:chemically induced / Q000473:pathology*; D049109:Cell Proliferation / Q000502:physiology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009765:Obesity / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D015431:Weight Loss / Q000502:physiology*
D001397:Azoxymethane
azoxymethane-induced carcinogenesis; colon carcinogenesis; liver pathology; obesity; weight loss