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Trans Fatty Acids Suppress TNF-α-Induced Inflammatory Gene Expression in Endothelial (HUVEC) and Hepatocellular Carcinoma (HepG2) Cells

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Lipids

Abstract

Trans fatty acids (TFA) intake has been linked to cardiovascular diseases and liver diseases; yet the effect of TFA on inflammation remains controversial. Accordingly, the objective of this paper was to determine the in vitro effects of TFA on inflammatory gene expression. Human umbilical vein endothelial cells (HUVEC) and human hepatocellular carcinoma (HepG2) cells were treated for 24 h with either trans-vaccenic acid (tVA), trans-palmitoleic acid (tPA) or elaidic acid (EA) at concentrations of 5–150 µM, or with a mixture of tVA and tPA (150/50 µM). All TFA were highly incorporated into cell membranes, as determined by gas chromatography, representing 15–20% of total fatty acids in HUVEC and 3–8% in HepG2 cells. Incorporation of EA, a common industrial TFA, increased the ratio of the stearoyl-CoA desaturase (SCD-1), a key enzyme involved in fatty acid metabolism. Ruminant TFA, including tVA, tPA and the mixture of tVA and tPA, significantly reduced the TNF-α-induced gene expression of TNF, VCAM-1 and SOD2 in HUVEC, as well as TNF and IL-8 in HepG2 cells. EA also decreased inflammatory gene expression in HUVEC, but not in HepG2 cells. The inhibition of peroxisome proliferator-activated receptor (PPAR)-γ did not influence the effects of TFA on gene expression. Overall, physiological and supraphysiological concentrations of TFA, especially tVA and tPA, prevented inflammatory gene expression in vitro. This effect is independent of PPAR-γ activation and may be due to an alteration of fatty acid metabolism in cell membranes caused by the high incorporation of TFA.

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Abbreviations

CVD:

Cardiovascular disease

DMSO:

Dimethyl sulfoxide

EA:

Elaidic acid

eNOS:

Endothelial nitric oxide synthase

HepG2:

Liver hepatocellular cells

HUVEC:

Human umbilical vein endothelial cells

IL:

Interleukin

iTFA:

Industrial TFA

LC–MS/MS:

Liquid chromatography coupled with tandem mass spectrometry

NF-κB:

Nuclear factor κB

NO:

Nitric oxide

PG:

Prostaglandin

PPAR:

Peroxisome proliferator-activated receptor

rTFA:

Ruminant TFA

SOD:

Superoxide dismutase

TFA:

Trans fatty acids

TNF-α:

Tumor necrosis factor alpha

tPA:

trans-Palmitoleic acid

tVA:

trans-Vaccenic acid

VCAM-1:

Vascular cell adhesion molecule 1

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Acknowledgements

The authors would like to thank Line Berthiaume, who performed gas chromatographic analyses to determine fatty acid profiles, as well as Jessica Larose and Karine Greffard for the determination of PGE2 levels by LC–MS/MS. The authors also thank Mélanie Verreault for useful assistance with the HepG2 cell culture. This study was supported by a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC). M.S.D.S. has received scholarships from the Centre de recherche en endocrinologie moléculaire et oncologique et génomique humaine (CREMOGH), the department of kinesiology of Université Laval and the CHU de Québec Foundation—Desjardins. I.R. holds a Junior 1 Research Scholar award from the Fonds de Recherche du Québec—Santé (FRQ-S).

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Authors and Affiliations

  1. Endocrinology and Nephrology Unit, Centre de recherche du CHU de Québec, Université Laval, 2705, boul. Laurier, Québec City, QC, G1V 4G2, Canada

    Marine S. Da Silva, Pierre Julien, Jean-François Bilodeau & Iwona Rudkowska

  2. The Department of Kinesiology, Faculty of Medicine, Université Laval, 2325 rue de l’Université, Québec City, QC, G1V 0A6, Canada

    Marine S. Da Silva & Iwona Rudkowska

  3. The Department of Medicine, Faculty of Medicine, Université Laval, 2325 rue de l’Université, Québec City, QC, G1V 0A6, Canada

    Pierre Julien & Jean-François Bilodeau

  4. Laboratory of Molecular Pharmacology, Centre de recherche du CHU de Québec, Université Laval, 2705, boul. Laurier, Québec City, QC, G1V 4G2, Canada

    Olivier Barbier

  5. The Faculty of Pharmacy, Université Laval, 2325 rue de l’Université, Québec City, QC, G1V 0A6, Canada

    Olivier Barbier

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  1. Marine S. Da Silva
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  2. Pierre Julien
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Correspondence to Iwona Rudkowska.

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Da Silva, M.S., Julien, P., Bilodeau, JF. et al. Trans Fatty Acids Suppress TNF-α-Induced Inflammatory Gene Expression in Endothelial (HUVEC) and Hepatocellular Carcinoma (HepG2) Cells. Lipids 52, 315–325 (2017). https://doi.org/10.1007/s11745-017-4243-4

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