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α-Linolenic acid suppresses cholesterol and triacylglycerol biosynthesis pathway by suppressing SREBP-2, SREBP-1a and -1c expression

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Abstract

α-Linolenic acid (ALA), a major fatty acid in flaxseed oil, has multiple functionalities such as anti-cardiovascular and anti-hypertensive activities. In this study, we investigated the effects of ALA on lipid metabolism and studied the possible mechanisms of its action in differentiated 3T3-L1 adipocytes using DNA microarray analysis. From a total of 34,325 genes in the DNA chip, 87 genes were down-regulated and 185 genes were up-regulated at least twofold in differentiated 3T3-L1 adipocyte cells treated with 300 μM ALA for a week, 5–12 days after induction of cell differentiation, compared to ALA-untreated 3T3-L1 adipocytes (control). From the Reactome analysis results, eight lipid metabolism-related genes involved in cholesterol and triacylglycerol biosynthesis pathway and lipid transport were significantly down-regulated by ALA treatment. Furthermore, ALA significantly decreased the mRNA expressions of sterol regulatory element binding protein (SREBP)-2, SREBP-1a, SREBP-1c and fatty acid synthase (FAS) in 3T3-L1 adipocyte cells. On the other hand, the average levels of the gene expressions of carnitine palmitoyltransferase 1a (CPT-1a) and leptin in 300 μM ALA treatment were increased by 1.7- and 2.9-fold, respectively, followed by an increase in the intracellular ATP content. These results show that ALA is likely to inhibit cholesterol and fatty acid biosynthesis pathway by suppressing the expression of transcriptional factor SREBPs. Furthermore, ALA promotes fatty acid oxidation in 3T3-L1 adipocytes, thereby increasing its health benefits.

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Abbreviations

ALA:

α-Linolenic acid

CPT-1a:

Carnitine palmitoyltransferase 1a

PUFAs:

Polyunsaturated fatty acids

EPA:

Eicosapentaenoic acid

DHA:

Docosahexaenoic acid

SREBP:

Sterol regulatory element binding protein

FAS:

Fatty acid synthase

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

Fetal bovine serum

SRE:

Sterol regulatory element

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Acknowledgments

We are grateful to all the members of the Isoda Laboratory (University of Tsukuba, Ibaraki, Japan) and Central Laboratory (Nippon Flour Mills Co., Ltd., Kanagawa, Japan) for their scientific input and contributions.

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Authors and Affiliations

  1. Central Laboratory, Nippon Flour Mills Co., Ltd., Midorigaoka, Atsugi, Kanagawa, Japan

    Satoshi Fukumitsu & Kazuhiko Aida

  2. Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Satoshi Fukumitsu, Junkyu Han & Hiroko Isoda

  3. Alliance for Research on North Africa (ARENA), University of Tsukuba, Tsukuba, Ibaraki, Japan

    Myra O. Villareal, Shoko Onaga, Junkyu Han & Hiroko Isoda

Authors
  1. Satoshi Fukumitsu
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  2. Myra O. Villareal
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  3. Shoko Onaga
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  4. Kazuhiko Aida
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  5. Junkyu Han
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  6. Hiroko Isoda
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Correspondence to Hiroko Isoda.

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Fukumitsu, S., Villareal, M.O., Onaga, S. et al. α-Linolenic acid suppresses cholesterol and triacylglycerol biosynthesis pathway by suppressing SREBP-2, SREBP-1a and -1c expression. Cytotechnology 65, 899–907 (2013). https://doi.org/10.1007/s10616-012-9510-x

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  • DOI: https://doi.org/10.1007/s10616-012-9510-x

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