TY - JOUR
T1 - Expression of the selenoprotein S (SELS) gene in subcutaneous adipose tissue and SELS genotype are associated with metabolic risk factors
AU - Olsson, Maja
AU - Olsson, Bob
AU - Jacobson, Peter
AU - Thelle, Dag S.
AU - Björkegren, Johan
AU - Walley, Andrew
AU - Froguel, Philippe
AU - Carlsson, Lena M.S.
AU - Sjöholm, Kajsa
N1 - Funding Information:
We thank Margareta Jernås and Johanna Andersson for running the microarrays, Jenny Palming for help with adipocyte isolation and incubation, Elisabeth Strandhagen for providing INTERGENE samples and data, and the Genomics Core Facility platform at the Sahlgrenska Academy, University of Gothenburg, which was funded by a grant from the Knut and Alice Wallenberg Foundation.
Funding Information:
This work was supported by grants from the Swedish Research Council ( K2009-65X-15424-05 , K2010-55X-11285-13 ), the Swedish foundation for Strategic Research to Sahlgrenska Center for Cardiovascular and Metabolic Research, the Swedish Diabetes foundation , the Åke Wiberg foundation , the foundations of the National Board of Health and Welfare , the Jeansson foundations , the Magnus Bergvall foundation , the Tore Nilson foundation , the Royal Physiographic Society (Nilsson-Ehle foundation) , the VINNOVA-VINNMER program , the Swedish federal government under the LUA/ALF agreement, the Swedish Knowledge Foundation through the Industrial PhD program in Medical Bioinformatics at Corporate Alliances, Karolinska Institutet, and the Wellcome Trust ( GR079534 ).
PY - 2011/1
Y1 - 2011/1
N2 - The selenoprotein S (SELS) is a putative receptor for serum amyloid A, and recent studies have suggested that SELS may be a link between type 2 diabetes mellitus and inflammation. Genetic studies of SELS polymorphisms have revealed associations with circulating levels of inflammatory markers and hard end points of cardiovascular disease. In this study, we analyzed SELS expression in subcutaneous adipose tissue and SELS genotype in relation to metabolic risk factors. DNA microarray expression analysis was used to study the expression of SELS in lean and obese siblings from the Swedish Obese Subjects Sib Pair Study. TaqMan genotyping was used to analyze 3 polymorphisms, previously found to be associated with circulating levels of inflammatory markers, in the INTERGENE case-control study of myocardial infarction and unstable angina pectoris. Possible associations between SELS genotype and/or expression with anthropometry and measures of metabolic status were investigated. Real-time polymerase chain reaction was used to analyze the SELS expression in isolated human adipocytes incubated with insulin. In lean subjects, we found correlations between SELS gene expression in subcutaneous adipose tissue and measures of obesity (waist, P = .045; sagittal diameter, P = .031) and blood pressure (diastolic, P = .016; systolic P = .015); and in obese subjects, we found correlations with measures of obesity (body mass index, P = .03; sagittal diameter, P = .008) and glycemic control (homeostasis model assessment of insulin resistance, P = .011; insulin, P = .009) after adjusting for age and sex. The 5227GG genotype was associated with serum levels of insulin (P = .006) and homeostasis model assessment of insulin resistance (P = .007). The expression of SELS increased after insulin stimulation in isolated human adipocytes (P = .008). In this study, we found an association between both SELS gene expression in adipose tissue and SELS genotype with measures of glycemic control. In vitro studies demonstrated that the SELS gene is regulated by insulin in human subcutaneous adipocytes. This study further supports a role for SELS in the development of metabolic disease, especially in the context of insulin resistance.
AB - The selenoprotein S (SELS) is a putative receptor for serum amyloid A, and recent studies have suggested that SELS may be a link between type 2 diabetes mellitus and inflammation. Genetic studies of SELS polymorphisms have revealed associations with circulating levels of inflammatory markers and hard end points of cardiovascular disease. In this study, we analyzed SELS expression in subcutaneous adipose tissue and SELS genotype in relation to metabolic risk factors. DNA microarray expression analysis was used to study the expression of SELS in lean and obese siblings from the Swedish Obese Subjects Sib Pair Study. TaqMan genotyping was used to analyze 3 polymorphisms, previously found to be associated with circulating levels of inflammatory markers, in the INTERGENE case-control study of myocardial infarction and unstable angina pectoris. Possible associations between SELS genotype and/or expression with anthropometry and measures of metabolic status were investigated. Real-time polymerase chain reaction was used to analyze the SELS expression in isolated human adipocytes incubated with insulin. In lean subjects, we found correlations between SELS gene expression in subcutaneous adipose tissue and measures of obesity (waist, P = .045; sagittal diameter, P = .031) and blood pressure (diastolic, P = .016; systolic P = .015); and in obese subjects, we found correlations with measures of obesity (body mass index, P = .03; sagittal diameter, P = .008) and glycemic control (homeostasis model assessment of insulin resistance, P = .011; insulin, P = .009) after adjusting for age and sex. The 5227GG genotype was associated with serum levels of insulin (P = .006) and homeostasis model assessment of insulin resistance (P = .007). The expression of SELS increased after insulin stimulation in isolated human adipocytes (P = .008). In this study, we found an association between both SELS gene expression in adipose tissue and SELS genotype with measures of glycemic control. In vitro studies demonstrated that the SELS gene is regulated by insulin in human subcutaneous adipocytes. This study further supports a role for SELS in the development of metabolic disease, especially in the context of insulin resistance.
UR - http://www.scopus.com/inward/record.url?scp=78649906119&partnerID=8YFLogxK
U2 - 10.1016/j.metabol.2010.05.011
DO - 10.1016/j.metabol.2010.05.011
M3 - Article
C2 - 20619427
AN - SCOPUS:78649906119
SN - 0026-0495
VL - 60
SP - 114
EP - 120
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 1
ER -