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ARS Home » Plains Area » Miles City, Montana » Livestock and Range Research Laboratory » Research » Publications at this Location » Publication #226250
Title: Comparative understanding of UTS2 and UTS2R genes for their involvement in type 2 diabetes mellitus

Author
item JIANG, ZHIHUA - WASHINGTON STATE U
item MICHAL, JENNIFER - WASHINGTON STATE U
item TOBEY, DAVID - WASHINGTON STATE U
item WANG, ZEPING - WASHINGTON STATE U
item Macneil, Michael
item MAGNUSON, NANCY - WASHINGTON STATE U

Submitted to: International Journal of Biological Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/30/2008
Publication Date: 5/30/2008
Citation: Jiang, Z., Michal, J.J., Tobey, D., Wang, Z., MacNeil, M.D., Magnuson, N.S. 2008. Comparative understanding of UTS2 and UTS2R genes for their involvement in type 2 diabetes mellitus. International Journal of Biological Sciences 4(2):96-102.

Interpretive Summary: Three members of the urotensin II family of peptides have been discovered in mammals, including urotensin 2 (UTS2), urotensin 2 receptor (UTS2R). Both UTS2 and UTS2R have been reported to affect glucose metabolism and insulin resistance, a core pathological characteristic of patients with type 2 diabetes mellitus. Studies have shown that the fat droplets accumulated in human skeletal muscle are a major contributor to insulin resistance. Therefore, the objective of the present study was to determine whether both UTS2 and UTS2R genes contribute to muscle lipid metabolism, using cattle as a model organism. We annotated both bovine UTS2 and UTS2R genes and identified 5 single nucleotide polymorphisms 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, 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, '9 desaturase activity for converting 16:0 into 16:1, muscle fat (marbling) score and Longissimus Dorsi muscle area. However, 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, this is 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 type 2 diabetes mellitus in humans.

Technical Abstract: 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, '9 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.