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Early obesity leads to increases in hepatic arginase I and related systemic changes in nitric oxide and l-arginine metabolism in mice

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Abstract

Obesity is a risk factor for vascular endothelial cell dysfunction characterized by low-grade, chronic inflammation. Increased levels of arginase I and concomitant decreases in l-arginine bioavailability are known to play a role in the pathogenesis of vascular endothelial cell dysfunction. In the present study, we focused on changes in the systemic expression of arginase I as well as l-arginine metabolism in the pre-disease state of early obesity prior to the onset of atherosclerosis. C57BL/6 mice were fed a control diet (CD; 10% fat) or high-fat diet (HFD; 60% fat) for 8 weeks. The mRNA expression of arginase I in the liver, adipose tissue, aorta, and muscle; protein expression of arginase I in the liver and plasma; and systemic levels of l-arginine bioavailability and NO2 − were assessed. HFD-fed mice showed early obesity without severe disease symptoms. Arginase I mRNA and protein expression levels in the liver were significantly higher in HFD-fed obese mice than in CD-fed mice. Arginase I levels were slightly increased, whereas l-arginine levels were significantly reduced, and these changes were followed by reductions in NO2 − levels. Furthermore, hepatic arginase I levels positively correlated with plasma arginase I levels and negatively correlated with l-arginine bioavailability in plasma. These results suggested that increases in the expression of hepatic arginase I and reductions in plasma l-arginine and NO2 − levels might lead to vascular endothelial dysfunction in the pre-disease state of early obesity.

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Funding

This work was supported in part by JSPS KAKENHI, a Grant-in-Aid for Science Research (C) (No. 15K08775) to MK, and a Grant-in-Aid for Science Research (B) (No. 26293152) to KO.

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Author notes

  1. Tatsuo Ito and Masayuki Kubo contributed equally to this work.

Authors and Affiliations

  1. Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Tatsuo Ito, Masayuki Kubo, Kenjiro Nagaoka, Heri Setiawan, Kei Takemoto, Eri Eguchi & Keiki Ogino

  2. Department of Epidemiology, Fukushima Prefectural Medical University, Fukushima, Japan

    Narumi Funakubo

  3. Department of Molecular Anatomy, Faculty of Medicine, Oita University, Yufu, Japan

    Yoshihisa Fujikura

Authors
  1. Tatsuo Ito
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  2. Masayuki Kubo
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  3. Kenjiro Nagaoka
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  4. Narumi Funakubo
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  6. Kei Takemoto
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  7. Eri Eguchi
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  8. Yoshihisa Fujikura
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  9. Keiki Ogino
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Corresponding author

Correspondence to Keiki Ogino.

Ethics declarations

The care and handling of animals were in accordance with the Guidelines for the Care and Use of Laboratory Animals at the Shikata Campus of Okayama University. This animal study was approved by the Okayama University Institutional Animal Care and Use Committee (OKU-2014322).

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Ito, T., Kubo, M., Nagaoka, K. et al. Early obesity leads to increases in hepatic arginase I and related systemic changes in nitric oxide and l-arginine metabolism in mice. J Physiol Biochem 74, 9–16 (2018). https://doi.org/10.1007/s13105-017-0597-6

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  • DOI: https://doi.org/10.1007/s13105-017-0597-6

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