The Increased Protein Level of URAT1 was Observed in Obesity/Metabolic Syndrome Model Mice

Abstract

To elucidate the mechanism of obesity/metabolic syndrome-related hyperuricemia, this study aimed to determine the expression levels of transport systems for urate absorption (Urat1, Smct1, Glut9) and urate secretion (Abcg2). The kidneys of two obesity models in mice were used: 1) leptin-deficient mice (ob/ob mice) and 2) Quick fat diet model.

1) 8-week-old male ob/ob mice demonstrated the increased protein levels of Slc22a12 (Urat1), Slc2a9 (Glut9), and Abcg2 (Abcg2) and a decreased protein level of Slc5a8 (Smct1). However, no significant changes in the mRNA levels of these genes were observed.

2) C57BL/6 mice were fed with a Quick fat diet (crude fat content: 13.6%) from the age of 24 to 28 weeks (Quick fat diet group). The average body weights of the Quick fat diet group were heavier than those of the control group fed with a normal diet (crude fat content: 4.8%). The mRNA levels of Slc22a12, Slc2a9, Abcg2, or Slc5a8 did not change significantly in both groups. The protein levels of Slc22a12 (Urat1) and Abcg2 (Abcg2) increased significantly in the Quick fat diet group. Those of Slc2a9 (Glut9) and Slc5a8 (Smct1) were not changed significantly in the Quick fat diet group.

In conclusion, the Quick fat diet enhanced the protein levels of Urat1 and Abcg2 without any changes in their mRNA transcription levels. The cause of obesity/metabolic syndrome-associated hyperuricemia appears to be associated with the urate reabsorption transporter Urat1 protein enhanced by fat.

Keywords:

• Transporter
• expression level
• fat

Acknowledgments

The authors thank Sumire Asanuma for technical assistance. This study was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (Grant 20590547).