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J Physiol Biochem. 2018 Feb;74(1):9-16. doi: 10.1007/s13105-017-0597-6. Epub 2017 Nov 3.

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

Author information

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.
2
Department of Epidemiology, Fukushima Prefectural Medical University, Fukushima, Japan.
3
Department of Molecular Anatomy, Faculty of Medicine, Oita University, Yufu, Japan.
4
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. kogino@md.okayama-u.ac.jp.

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.

KEYWORDS:

Arginase; L-Arginine metabolism; Nitric oxide; Obesity; Pre-disease state

PMID:
29098611
DOI:
10.1007/s13105-017-0597-6
[Indexed for MEDLINE]

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