Journal article
Dietary Fats High in Linoleic Acids Impair Antitumor T-cell Responses by Inducing E-FABP-Mediated Mitochondrial Dysfunction
Cancer research (Chicago, Ill.), Vol.81(20), pp.5296-5310
10/15/2021
DOI: 10.1158/0008-5472.CAN-21-0757
PMCID: PMC8530923
PMID: 34400394
Abstract
The most recent American Dietary Guidelines (2020-2025) recommend shifting dietary fats from solid saturated fats to unsaturated oils. Dietary oils contain different compositions of unsaturated fatty acids (UFA). Oleic acid (OA) and linoleic acid (LA) are the most common UFA in dietary oils. How individual UFA in oils regulate immune cell function and cancer risk remains unclear. Here we demonstrated that high-fat diets (HFD) rich either in OA or LA induced a similar degree of murine obesity, but the LA-rich HFD specifically promoted mammary tumor growth. LA impaired antitumor T-cell responses by promoting naive T-cell apoptosis and inhibiting TNF alpha production. While exogenous OA and LA were taken up by T cells with similar efficacy, only LA induced significant mitochondrial reactive oxygen species production and lipid peroxidation. Importantly, naive T cells predominantly expressed epidermal fatty acid binding protein (E-FABP), which is central in facilitating LA mitochondrial transport and cardiolipin incorporation. Genetic depletion of E-FABP rescued LA-impaired T-cell responses and suppressed LA-rich HFD-associated mammary tumor growth. Collectively, these data suggest that dietary oils high in LA promote mammary tumors by inducing E-FABP-mediated T-cell dysfunction. Significance: These findings suggest that modulation of dietary oil composition and inhibition of E-FABP activity may represent novel strategies to enhance T-cell function in the prevention and treatment of obesity-associated cancers.
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Details
- Title: Subtitle
- Dietary Fats High in Linoleic Acids Impair Antitumor T-cell Responses by Inducing E-FABP-Mediated Mitochondrial Dysfunction
- Creators
- Rong Jin - University of LouisvilleJiaqing Hao - University of LouisvilleYanmei Yi - University of LouisvilleDi Yin - University of LouisvilleYuan Hua - University of LouisvilleXiaohong Li - University of LouisvilleHanmei Bao - The University of Texas Health Science Center at San AntonioXianlin Han - The University of Texas Health Science Center at San AntonioNejat K. Egilmez - University of LouisvilleEdward R. Sauter - Center for Cancer ResearchBing Li - University of Louisville
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.81(20), pp.5296-5310
- DOI
- 10.1158/0008-5472.CAN-21-0757
- PMID
- 34400394
- PMCID
- PMC8530923
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 15
- Grant note
- NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01CA180986; R01AI137324 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Functional Microbiomics Core at the University of Louisville Aging Studies, University of Texas Health Science Center at San Antonio
- Language
- English
- Date published
- 10/15/2021
- Academic Unit
- Pathology; Surgery
- Record Identifier
- 9984695792602771
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