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Interactive Effects of Omega-3 Polyunsaturated Fatty Acids and Secondhand Smoke in Mice and Human Subjects

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Abstract

Active smoking and secondhand smoke (SHS) exposure increase the risk of cardiovascular morbidity and mortality. Active smoking is associated with reduced levels of omega-3 polyunsaturated fatty acids (n-3 PUFA) and studies show that n-3 PUFA supplementation can improve smoking-induced vascular dysfunction. However, the relationship between n-3 PUFA and SHS exposure has not been studied. Fat-1 transgenic mice, which convert n-6 to n-3 PUFA, were fed diets with n-3 PUFA or without (n-6 PUFA diet), exposed to air or SHS for 4 weeks, and vasoreactivity, antioxidant indices, and omega-3 index (percent eicosapentaenoic + docosahexaenoic acids in RBC) measured. Compared to air-exposed mice, SHS-enhanced aortic constriction in mice fed the n-6 PUFA diet (omega-3 index, 5.9 ± 0.2%; mean ± SE), but not in mice fed the n-3 PUFA diet (omega-3 index, 7.8 ± 0.6%). SHS also significantly induced mRNA expression of cytochrome P4501A1, NADPH:quinone oxidoreductase, heme oxygenase-1, and angiotensinogen in adipose tissue, and increased antioxidant capacity only in mice on the n-6 PUFA diet. Notably, SHS reduced the omega-3 index by 1.0 percentage point (p = 0.003), compared to air-exposed mice irrespective of diet. Additionally, we recruited human nonsmokers (NS) with and without SHS exposure (n = 40) 19–40 years old and measured the omega-3 index and antioxidant capacity. In human subjects SHS exposure was associated with a significantly lower omega-3 index (NS, 4.4 ± 1.1%; NS + SHS, 3.2 ± 1.0%; mean ± SD, p = 0.002) and higher antioxidant capacity (p < 0.001) than unexposed NS. Thus, SHS exposure is associated with lower levels of n-3 PUFA in mice and humans; however, an omega-3 index of ~ 8% in mice has vasoprotective and antioxidant properties.

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Data Availability

Upon acceptance of this manuscript, the data presented herein will be deposited in the University of New Mexico Digital Repository https://digitalrepository.unm.edu/

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Acknowledgements

We would like to thank the Clinical and Translational Center staff, including Susan Tigert, Michelle Jimenez, Abigail Cunningham, Adriana Villalobos, Hunter Esmiol, and Dominique Spence for their excellent technical support. This research was support by the National Institutes of Health (R15HL130970) and by the UNM Clinical and Translational Science Center (UL1TR001449) to M.K.W. and J.R.A.

Funding

This research was support by the National Institutes of Health (R15HL130970) and by the UNM Clinical and Translational Science Center (UL1TR001449) to M.K.W. and J.R.A.

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  1. Emily Wheeler

    Present address: National Jewish Health, Denver, CO, 80206, USA

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  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, 2703 Frontier Ave NE MSC09 5630, Albuquerque, NM, 87131, USA

    Emily Wheeler, Mary Walsh-Wilcox, Meera Shah & Mary K. Walker

  2. Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM, 87131, USA

    Abinash Achrekar

  3. Department of Pharmacy Practice and Administrative Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA

    Joe R. Anderson

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The experimental animal portion of this study was approved by the University of New Mexico Institutional Animal Care and Use Committee. The human subjects portion of this study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving human subjects were approved by the University of New Mexico Institutional Review Board (HRRC: 15–033).

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Wheeler, E., Walsh-Wilcox, M., Shah, M. et al. Interactive Effects of Omega-3 Polyunsaturated Fatty Acids and Secondhand Smoke in Mice and Human Subjects. Cardiovasc Toxicol 21, 115–126 (2021). https://doi.org/10.1007/s12012-020-09601-6

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