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In-Vitro Toxicological and Proteomic Analysis of Furan Fatty Acids Which are Oxidative Metabolites of Conjugated Linoleic Acids

  • Original Article
  • Published:
Lipids

Abstract

Furan fatty acids (furan-FA) are oxidative products of conjugated linoleic acids (CLA) and may therefore be ingested when CLA-containing food or food-additives are consumed. Due to the presence of a furan ring structure the question arises whether furan-FA may have toxic properties on enterocytes and liver cells. Here we show that furan-FA neither have toxic effects in human colon cancer cell line Caco-2 nor in human hepatoma cell line HepG2 at concentrations that could be relevant for humans. At concentrations up to 100 μM, all tested furan-FA isomers showed no pronounced cytotoxicity and did not affect cellular proliferation or apoptosis up to concentrations of 500 μM. In addition, furan-FA was neither genotoxic in the micronucleus test using Chinese hamster lung fibroblasts (V79) nor in the Ames test independent of the presence or absence of rat liver homogenate for enzymatic activation of the furan ring structure. A proteomic approach revealed that 48 proteins were differentially expressed when Caco-2 cells were incubated with up to 1 mM of 10,13-epoxy-10,12-octadecadienoic acid (10,12-furan-FA). Three of the 30 proteins that could be identified by MALDI-TOF analysis were upregulated and were associated with lipid droplet biogenesis. The remaining 27 proteins were downregulated and were considered to be associated with general cellular processes such as DNA replication and transcription, protein biosynthesis and protein processing, lipid and energy metabolism. From the proteomic data we conclude that furan-FA is predominantly stored in lipid droplets thereby downregulating cellular metabolic activity and driving the cells into a state of rest.

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Abbreviations

2-DE:

Two-dimensional polyacrylamide gel electrophoresis

CLA:

Conjugated linoleic acid

Furan-FA:

Furan fatty acid

IEF:

Isoelectric focusing

IPG:

Immobilized pH gradient

MALDI-TOF:

Matrix-assisted laser desorption ionisation-time of flight

ER:

Endoplasmic reticulum

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Acknowledgments

We thank Linda Brandenburger, Brigitte Finke, Anja Köllner, Christine Meckert, and Marlies Sagmeister for technical assistance. This work was funded by the Deutsche Forschungsgemeinschaft (DFG project LA 1177/5-4).

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Authors and Affiliations

  1. Department of Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany

    Imme Lengler, Thorsten Buhrke, Eileen Scharmach & Alfonso Lampen

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  1. Imme Lengler
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  2. Thorsten Buhrke
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  4. Alfonso Lampen
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Correspondence to Thorsten Buhrke.

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Lengler, I., Buhrke, T., Scharmach, E. et al. In-Vitro Toxicological and Proteomic Analysis of Furan Fatty Acids Which are Oxidative Metabolites of Conjugated Linoleic Acids. Lipids 47, 1085–1097 (2012). https://doi.org/10.1007/s11745-012-3713-y

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