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

• Tatsuo Ito ^[1] ; Keiki Ogino ^[1] ; Masayuki Kubo ^[1] ; Kenjiro Nagaoka ^[1] ; Narumi Funakubo ^[2] ; Heri Setiawan ^[1] ; Kei Takemoto ^[1] ; Eri Eguchi ^[1] ; Yoshihisa Fujikura ^[3]
  1. [1] Okayama University

     Okayama University

     Naka-ku, Japón

     
  2. [2] Fukushima Prefectural Medical UniversityFukushimaJapan
  3. [3] Faculty of MedicineOita UniversityYufuJapan

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• Localización: Journal of physiology and biochemistry, ISSN-e 1877-8755, ISSN 1138-7548, Vol. 74, Nº. 1, 2018, págs. 9-16
• Idioma: inglés
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• Resumen

  • 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.