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Free Fatty Acids Increase Intracellular Lipid Accumulation and Oxidative Stress by Modulating PPARα and SREBP-1c in L-02 Cells

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Lipids

Abstract

Excessive fat accumulation and increased oxidative stress contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the development of steatosis are not entirely understood. The present study was undertaken to establish an experimental model of hepatocellular steatosis with a fat overaccumulation profile in which the effects of oxidative stress could be studied in L-02 cells. We investigated the effects of free fatty acids (FFA) (palmitate:oleate, 1:2) on lipid accumulation and oxidative stress and their possible mechanisms in L-02 cells. High concentrations of fatty acids significantly induced excessive lipid accumulation and oxidative stress in L-02 cells, which could only be reversed with 50 μΜ WY14643 (the PPARα agonist). Immunoblotting and qPCR analyses revealed that FFA downregulated the expression of proliferator-activated receptor alpha (PPARα), which contributed to the increased activation of sterol regulatory element binding protein-1c (SREBP-1c). These results suggest that FFA induce lipid accumulation and oxidative stress in L-02 cells by upregulating SREBP-1c expression through the suppression of PPARα.

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Abbreviations

NAFLD:

Nonalcoholic fatty liver disease

FFA:

Free fatty acids

PPARα:

Proliferator-activated receptor alpha

SREBP-1c:

Sterol regulatory element binding protein-1c

LDH:

Lactate dehydrogenase

ROS:

Reactive oxygen species

GSH:

Glutathione

SOD:

Superoxide dismutase

DCFH-DA:

2′-7′-Dichlorofluorescein diacetate

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Acknowledgments

This study was supported by grants from the Natural Science Foundation of China (No. 81274160), the Natural Science Foundation of Guangdong Province (No. S2012010009380) and the Science and Technology Development project of Guangdong province (No. 2010B060900056).

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Authors and Affiliations

  1. Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China

    Shumin Qin

  2. Department of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, People’s Republic of China

    Jinjin Yin

  3. The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China

    Keer Huang

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  1. Shumin Qin
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  2. Jinjin Yin
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  3. Keer Huang
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Correspondence to Keer Huang.

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The authors declare that there are no conflicts of interest.

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Qin, S., Yin, J. & Huang, K. Free Fatty Acids Increase Intracellular Lipid Accumulation and Oxidative Stress by Modulating PPARα and SREBP-1c in L-02 Cells. Lipids 51, 797–805 (2016). https://doi.org/10.1007/s11745-016-4160-y

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  • DOI: https://doi.org/10.1007/s11745-016-4160-y

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