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.

Fasting plasma glucose and serum uric acid levels in a general Chinese population with normal glucose tolerance: A U-shaped curve

“…Thus, it is hypothesized that insulin could activate renal uric reabsorption through sodium-dependent anion transporters in brush-border membranes of the renal proximal tubule [4], since evidence for a direct effect of insulin on natriuresis has obtained both in normal subjects and in patients with essential hypertension [46]. In addition, high serum insulin levels may enhance renal uric acid reabsorption through elevated expression of the urate transporter-1, which is a urate exchanger mediating urate movement from urine to epithelium [47, 48]. Furthermore, increase in insulin levels could promote xanthine dehydrogenase and purine nucleoside phosphorylase, which participates in uric acid synthesis and elevates the level of uric acid in serum [49].…”

Perbandingan Kadar Asam Urat Pada Subyek Obes Dan Non-Obes Di Fakultas Kedokteran Universitas Sam Ratulangi Manado

“…18 Dari hasil penelitian rata-rata kadar asam urat pada mahasiswa obes terlihat ada peningkatan asam urat di setiap pertambahan usia tetapi pada saat usia 21 tahun ada penurunan penelitian ini tidak sesuai dengan studi yang dilakukan oleh Pasifico EL et al tahun 2009 pada anak dan remaja menemukan bahwa hiperurisemia berhubungan erat dengan obesitas, lebih khusunya penderita sindroma metabolik. Selain itu, hiperurisemia berhubungan erat dengan jenis kelamin laki-laki dan pertambahan usia, [19][20] tetapi juga penelitian pada mahasiswa non obes terjadi peningkatan di setiap usia meskipun peningkatan itu tidak dikatakan sebagai hiperurisemia.…”

Endocrine and metabolic regulation of renal drug transporters

“…Analysis of kidney transporters in ob/ob mice revealed decreased mRNA and protein expression of Mrp3 in female mice, decreased Oatp1a1 and Oat2 mRNA expression, and increased Mrp4 mRNA and protein expression (103). In addition, the kidneys of ob/ob mice have increased expression of Bcrp, Urat1, and Glut9 protein and trends for elevated Bcrp and Glut9 mRNAs (104). This pattern of transporter regulation would favor enhanced secretion and reduced reabsorption of organic anions in TIID.…”