Int J Biol Sci 2008; 4(2):96-102. doi:10.7150/ijbs.4.96
Comparative understanding of UTS2 and UTS2R genes for their involvement in type 2 diabetes mellitus
1. Department of Animal Sciences, Washington State University, Pullman, WA 99164–6351, USA
2. School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4660, USA
3. USDA Agricultural Research Service Fort Keogh Livestock and Range Research Laboratory, Miles City, MT 59301, USA
Jiang Z, Michal JJ, Tobey DJ, Wang Z, MacNeil MD, Magnuson NS. Comparative understanding of UTS2 and UTS2R genes for their involvement in type 2 diabetes mellitus. Int J Biol Sci 2008; 4(2):96-102. doi:10.7150/ijbs.4.96. Available from http://www.ijbs.com/v04p0096.htm
Several reports have shown that urotensin 2 (UTS2) and its receptor (UTS2R) are involved in glucose metabolism and insulin resistance, which lead to development of type 2 diabetes mellitus (T2DM) in humans. In the present study, we annotated both bovine UTS2 and UTS2R genes and identified 5 single nucleotide polymorphisms (SNPs) for the former gene and 14 mutations for the latter gene. Four mutations were genotyped on a Wagyu x Limousin reference population, including 6 F1 bulls, 113 F1 dams and ~250 F2 progeny. Among 12 phenotypes related to fat deposition and fatty acid composition, we observed that the UTS2 gene was significantly associated with the amount of skeletal saturated fatty acids, while its receptor (UTS2R) gene had significant effects on amounts of saturated and monounsaturated fatty acids, Δ9 desaturase activity for converting 16:0 into 16:1, muscle fat (marbling) score and Longissimus Dorsi muscle area. However, in this population, these markers were not associated with subcutaneous fat depth or percent kidney, pelvic and heart fat. We also found that mutations in the promoter regions altered the promoter activities in both genes and coding SNPs might affect the mRNA stability in the UTS2R gene. Overall, our present study provides the first evidence that both UTS2 and UTS2R genes regulate skeletal muscle fat accumulation and fatty acid metabolism, thus indicating their potential pathological functions related to obesity and T2DM in humans.
Keywords: Type 2 diabetes mellitus, UTS2, UTS2R, skeletal fat accumulation, fatty acid composition.