Consumption of the Fish Oil High-Fat Diet Uncouples Obesity and Mammary Tumor Growth through Induction of Reactive Oxygen Species in Protumor Macrophages

Lianliang Liu; Rong Jin; Jiaqing Hao; Jun Zeng; Di Yin; Yanmei Yi; Mingming Zhu; Anita Mandal; Yuan Hua; Chin K Ng; Nejat K Egilmez; Edward R Sauter; Bing Li

doi:10.1158/0008-5472.CAN-19-3184

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Consumption of the Fish Oil High-Fat Diet Uncouples Obesity and Mammary Tumor Growth through Induction of Reactive Oxygen Species in Protumor Macrophages

Journal article

Open access

Peer reviewed

Consumption of the Fish Oil High-Fat Diet Uncouples Obesity and Mammary Tumor Growth through Induction of Reactive Oxygen Species in Protumor Macrophages

Lianliang Liu, Rong Jin, Jiaqing Hao, Jun Zeng, Di Yin, Yanmei Yi, Mingming Zhu, Anita Mandal, Yuan Hua, Chin K Ng, …

Cancer research (Chicago, Ill.), Vol.80(12), pp.2564-2574

06/15/2020

DOI: 10.1158/0008-5472.CAN-19-3184

PMCID: PMC7299802

PMID: 32213543

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https://doi.org/10.1158/0008-5472.CAN-19-3184View

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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 and . 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.

Animals

Carcinogenesis - immunology

Carcinogenesis - metabolism

Cell Line, Tumor - transplantation

Diet, High-Fat - adverse effects

Diet, High-Fat - methods

Dietary Fats - adverse effects

Fatty Acid-Binding Proteins - genetics

Fatty Acid-Binding Proteins - metabolism

Female

Fish Oils - administration & dosage

Humans

Macrophages - cytology

Macrophages - immunology

Macrophages - metabolism

Mammary Glands, Animal - cytology

Mammary Glands, Animal - immunology

Mammary Glands, Animal - pathology

Mammary Neoplasms, Experimental - genetics

Mammary Neoplasms, Experimental - immunology

Mammary Neoplasms, Experimental - metabolism

Mammary Neoplasms, Experimental - prevention & control

Mice

Mice, Knockout

Mitochondria - metabolism

Obesity - complications

Obesity - immunology

Obesity - metabolism

Primary Cell Culture

Reactive Oxygen Species - metabolism

Details

Title: Subtitle: Consumption of the Fish Oil High-Fat Diet Uncouples Obesity and Mammary Tumor Growth through Induction of Reactive Oxygen Species in Protumor Macrophages
Creators: Lianliang Liu - University of Louisville
Rong Jin - Peking University
Jiaqing Hao - University of Louisville
Jun Zeng - Guangzhou Medical University
Di Yin - Guangzhou Medical University
Yanmei Yi - Department of Histology and Embryology, Guangdong Medical University, Guangdong, China
Mingming Zhu - University of Louisville
Anita Mandal - University of Louisville
Yuan Hua - University of Louisville
Chin K Ng - University of Louisville
Nejat K Egilmez - University of Louisville
Edward R Sauter - Division of Cancer Prevention, NCI, NIH, Rockville, Maryland
Bing Li - University of Louisville
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.80(12), pp.2564-2574
DOI: 10.1158/0008-5472.CAN-19-3184
PMID: 32213543
PMCID: PMC7299802
ISSN: 0008-5472
eISSN: 1538-7445
Grant note: R01 CA180986 / NCI NIH HHS R01 CA177679 / NCI NIH HHS R01 AI137324 / NIAID NIH HHS
Language: English
Date published: 06/15/2020
Academic Unit: Pathology
Record Identifier: 9984203890802771

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