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Increased expression of acyl-CoA oxidase 2 in the kidney with plasma phytanic acid and altered gut microbiota in spontaneously hypertensive rats

Hypertension Research volume 44, pages 651–661 (2021)Cite this article

Abstract

We performed a DNA microarray analysis of the renal medulla and cortex from spontaneously hypertensive rats (SHRs), stroke-prone SHRs (SHRSPs), and Wistar–Kyoto (WKY) rats to identify pivotal molecules in the kidney associated with the onset of hypertension and found increased expression of acyl-CoA oxidase 2 (Acox2) mRNA. Real-time polymerase chain reaction revealed that Acox2 mRNA expression in the renal medulla and cortex of SHRs and SHRSPs was increased in comparison to WKY rats. These findings indicate that increased renal ACOX2 (an enzyme that induces the β-oxidation of fatty acids) is associated with the onset of hypertension. Immunostaining of ACOX2 in the distal tubules from SHRs was stronger than that in the distal tubules from WKY rats. Western blot analysis showed increased expression of ACOX2 protein in renal medulla from SHRs. Regarding the overexpression of ACOX2, plasma levels of phytanic acid in SHRs were significantly higher than those in WKY rats. There were no differences in other short-chain fatty acids. Plasma phytanic acid was affected by the gut microbiota through the conversion from phytol by yeast in the intestinal tract. We compared the gut microbiota profile in three strains of 5-week-old rats by the terminal-restriction fragment length polymorphism method. The gut microbiota profile and ratio of Firmicutes/Bacteroides differed between SHRs and WKY rats. These findings suggest that the increased expression of ACOX2 in the kidney along with increases in plasma phytanic acid and the altered gut microbiota may be involved in the oxidation in the kidney and the pathogenesis of hypertension.

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Acknowledgements

The authors would like to thank Akiko Tsunemi and Mayumi Katakawa for their technical support. The authors acknowledge the support of this study by financial grants from the MEXT-Supported Program for the Strategic Research Foundation at Private Universities (S1411018).

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Authors and Affiliations

  1. Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan

    Masahiro Okamura, Takahiro Ueno, Sho Tanaka, Yusuke Murata, Hiroki Kobayashi, Masanori Abe & Noboru Fukuda

  2. Laboratory of Clinical Pharmacokinetics, School of Pharmacy, Nihon University, Chiba, Japan

    Aoi Miyamoto

  3. Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan

    Noboru Fukuda

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  1. Masahiro Okamura
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  2. Takahiro Ueno
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  3. Sho Tanaka
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  4. Yusuke Murata
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  5. Hiroki Kobayashi
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  6. Aoi Miyamoto
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  7. Masanori Abe
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Correspondence to Masanori Abe or Noboru Fukuda.

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Okamura, M., Ueno, T., Tanaka, S. et al. Increased expression of acyl-CoA oxidase 2 in the kidney with plasma phytanic acid and altered gut microbiota in spontaneously hypertensive rats. Hypertens Res 44, 651–661 (2021). https://doi.org/10.1038/s41440-020-00611-z

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