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

Tatsuo Ito, Masayuki Kubo, Kenjiro Nagaoka, Narumi Funakubo, Heri Setiawan, Kei Takemoto, Eri Eguchi, Yoshihisa Fujikura, Keiki Ogino

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalJournal of Physiology and Biochemistry
DOIs
Publication statusAccepted/In press - Nov 3 2017

Keywords

  • Arginase
  • l-Arginine metabolism
  • Nitric oxide
  • Obesity
  • Pre-disease state

ASJC Scopus subject areas

  • Physiology
  • Biochemistry

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