TY - JOUR
T1 - Early obesity leads to increases in hepatic arginase I and related systemic changes in nitric oxide and l-arginine metabolism in mice
AU - Ito, Tatsuo
AU - Kubo, Masayuki
AU - Nagaoka, Kenjiro
AU - Funakubo, Narumi
AU - Setiawan, Heri
AU - Takemoto, Kei
AU - Eguchi, Eri
AU - Fujikura, Yoshihisa
AU - Ogino, Keiki
N1 - Funding Information:
Funding information 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.
Publisher Copyright:
© 2017, University of Navarra.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - Arginase
KW - Nitric oxide
KW - Obesity
KW - Pre-disease state
KW - l-Arginine metabolism
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U2 - 10.1007/s13105-017-0597-6
DO - 10.1007/s13105-017-0597-6
M3 - Article
C2 - 29098611
AN - SCOPUS:85032934073
VL - 74
SP - 9
EP - 16
JO - Revista Espanola de Fisiologia
JF - Revista Espanola de Fisiologia
SN - 1138-7548
IS - 1
ER -