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Daily Intake of High-Fat Diet with Lysophosphatidic Acid-Rich Soybean Phospholipids Augments Colon Tumorigenesis in Kyoto Apc Delta Rats

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Abstract

Background

Oral administration of lysophosphatidic acid (LPA) was shown to attenuate gastric ulceration in rats and mice but aggravate intestinal tumorigenesis in mice.

Aims

The present study examined whether dietary LPA induces or prevents development of colorectal tumor in rats.

Methods

Kyoto Apc Delta rats fed high-fat diet with or without an LPA-rich soybean phospholipid mixture (LSP, 0.1 or 1%) were treated with azoxymethane and dextran sodium sulfate to induce colorectal tumorigenesis. Rats were killed 15 weeks after azoxymethane treatment, and size, total number, location, and severity of colorectal tumors were assessed. Expression of mRNA of LPA receptors in rat colon tissue was assayed.

Results

Rats fed the diet supplemented with 1% LSP had a higher number of tumors 2–4 mm long compared than those with or without 0.1% LSP. The mean distance of tumors >4 mm long from the anus was significantly higher than those of tumors <2 and 2–4 mm long in rats fed 1% LSP-supplemented diet. Supplementation of the diet with 0.1% LSP decreased mRNA expression of LPA5 in colon tumors of rats.

Conclusions

Dietary supplementation of LPA-rich phospholipids dose-dependently augmented colorectal tumorigenesis. Decreased expression of LPA5 in colon tumors may be relevant to augmented tumorigenesis.

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Abbreviations

ACF:

Aberrant crypt foci

ATX:

Autotaxin

AOM:

Azoxymethane

Apc:

Adenomatous polyposis coli

DSS:

Dextran sodium sulfate

HF:

High-fat diet

KAD:

Kyoto Apc Delta

LPA:

Lysophosphatidic acid

LSP:

LPA-rich soybean phospholipid mixture

LPC:

Lysophosphatidylcholine

LPE:

Lysophosphatidylethanolamine

LPI:

Lysophosphatidylinositol

LPS:

Lysophosphatidylserine

TG:

Triglyceride

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Acknowledgments

The authors are grateful to Dr. Kenji Tsukigawa for tumor assessment, and Naoki Shirasaka for kindly providing a preparation of LPA-rich soybean phospholipid mixture.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshinomachi, Nobeoka, Japan

    Toshihiko Tsutsumi

  2. Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, 1-78-1 Shomachi, Tokushima, Japan

    Manami Inoue, Yoko Okamoto & Akira Tokumura

  3. Department of Anatomic Pathology, Prefectural Nobeoka Hospital, 2-1-10 Shinkoji, Nobeoka, Japan

    Akira Ishihara

  4. Department of Life Sciences, Faculty of Pharmacy, Yasuda Women’s University, 6-13-1 Yasuhigashi Asaminami-ku, Hiroshima, Japan

    Akira Tokumura

Authors
  1. Toshihiko Tsutsumi
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  2. Manami Inoue
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Correspondence to Toshihiko Tsutsumi.

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Tsutsumi, T., Inoue, M., Okamoto, Y. et al. Daily Intake of High-Fat Diet with Lysophosphatidic Acid-Rich Soybean Phospholipids Augments Colon Tumorigenesis in Kyoto Apc Delta Rats. Dig Dis Sci 62, 669–677 (2017). https://doi.org/10.1007/s10620-016-4434-5

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  • DOI: https://doi.org/10.1007/s10620-016-4434-5

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