Consumption of the Fish Oil High-Fat Diet Uncouples Obesity and Mammary Tumor Growth through Induction of Reactive Oxygen Species in Protumor Macrophages
Liu L, Liu L, Jin R, Hao J, Zeng J, Yin D, Yi Y, Zhu M, Mandal A, Hua Y, Ng CK, Egilmez NK, Sauter ER, Li B
Cancer research · 95 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- National Institutes of Health
- Government
- National Cancer Institute
- Government
- National Institute of Allergy and Infectious Diseases
- Government
- NIH
- Government
- NCI NIH HHS
- Government
- NIAID NIH HHS
- Grants
- National Cancer Institute (R01 CA177679); National Institute of Allergy and Infectious Diseases (R01 AI137324); National Cancer Institute (R01 CA180986); National Institutes of Health (R01CA177679); National Institutes of Health (R01CA180986); National Institutes of Health (R01AI137324)
Based on 6 listed funder(s).
Publication
- Published
- 2020-03-25 · Cancer Res · vol. 80 · issue 12 · pp. 2564–2574
- Publisher
- American Association for Cancer Research
- Cited
- 126 citations · more than 94% of similar papers · 3.3× the field average
- Impact
- Top 10% most cited in its field
- References
- 46 works
- Access
- Open access (repository copy)
- Research areas
- Peroxisome Proliferator-Activated Receptors · Cancer, Lipids, and Metabolism · Fatty Acid Research and Health
- Keywords
- Fish oil, Mammary tumor, Biology, Reactive oxygen species, Obesity, Macrophage, Cancer, Adipose tissue, Internal medicine, Physiology, Endocrinology, Immunology, Breast cancer, Medicine, Biochemistry, Fish <Actinopterygii>, In vitro
- MeSH
- mammary glands, animal, cell line, tumor, mitochondria, macrophages, animals, mice, knockout, humans, mice, mammary neoplasms, experimental, obesity, reactive oxygen species, dietary fats, fish oils, female, fatty acid-binding proteins, primary cell culture, diet, high-fat, carcinogenesis
13 authors
From CN, US
- Lianliang LiuNingbo University; University of Louisville
- Rong JinUniversity of Louisville; Peking University
- Jiaqing HaoUniversity of Louisville
- Jun ZengUniversity of Louisville; Guangzhou Medical University
- Di YinUniversity of Louisville; Guangzhou Medical University
- Yanmei YiUniversity of Louisville; Guangdong Medical College
Abstract
Obesity is associated with increased risk of many types of cancer and can be induced by various high-fat diets (HFD) from different fat sources. It remains unknown whether fatty acid composition in different HFD influences obesity-associated tumor development. Here we report that consumption of either a cocoa butter or fish oil HFD induced similar obesity in mouse models. While obesity induced by the cocoa butter HFD was associated with accelerated mammary tumor growth, consumption of the fish oil HFD uncoupled obesity from increased mammary tumor growth and exhibited a decrease in protumor macrophages. Compared with fatty acid (FA) components in both HFDs, n-3 FA rich in the fish oil HFD induced significant production of reactive oxygen species (ROS) and macrophage death. Moreover, A-FABP expression in the protumor macrophages facilitated intracellular transportation of n-3 FA and oxidation of mitochondrial FA. A-FABP deficiency diminished n-3 FA-mediated ROS production and macrophage death in vitro and in vivo. Together, our results demonstrate a novel mechanism by which n-3 FA induce ROS-mediated protumor macrophage death in an A-FABP-dependent manner. SIGNIFICANCE: This study provides mechanistic insight into dietary supplementation with fish oil for breast cancer prevention and advances a new concept that not all HFDs leading to obesity are tumorigenic. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/12/2564/F1.large.jpg.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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