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- Adewumi, Oluseun, et al.
(författare)
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Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
- 2007
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816
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Tidskriftsartikel (refereegranskat)abstract
- The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
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- Gertow, K., et al.
(författare)
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Fatty acid handling protein expression in adipose tissue, fatty acid composition of adipose tissue and serum, and markers of insulin resistance
- 2006
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 60:12, s. 1406-1413
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Proteins involved in cellular fatty acid (FA) uptake and metabolism may be of relevance in the context of disturbed FA metabolism associated with insulin resistance. Therefore this study investigated relationships between FA handling protein mRNA expression in adipose tissue, FA composition of adipose tissue and serum, and markers of insulin resistance. Subjects: 75 subjects with a range of insulin sensitivities recruited from a cohort of 294 healthy 63-year-old Swedish men. Measurements: Anthropometric and biochemical variables (e.g. waist-hip-ratio (WHR) and homeostasis model assessment (HOMA) index of insulin sensitivity), FA composition of the subcutaneous (s.c.) gluteal adipose tissue, serum nonesterified FA (NEFA) and serum phospholipid compartments (by gas-liquid chromatography; n = 294), and mRNA levels of FA handling proteins (adipocyte and keratinocyte lipid binding proteins, fatty acid transport protein (FATP) -1 and -4, CD36/fatty acid translocase, plasma membrane fatty acid binding protein, and acyl-CoA synthase-1 (ACS1)) in s.c. gluteal adipose tissue (by quantitative real-time polymerase chain reaction; n = 75). Results: ACS1 expression was negatively correlated with measures of insulin resistance and central obesity ( ACS1 versus HOMA: r = -0.28, P < 0.05; ACS1 versus WHR: r = -0.23, P < 0.05), with an opposite trend for FATP4. Further analysis of ACS1 expression levels revealed correlations with adipose tissue 16:0 (r = -0.27, P < 0.05) and NEFA 16: 1 (r = 0.29, P < 0.05), FA composition variables which in turn correlated with HOMA index (r = 0.39, P < 0.001 and r = -0.23, P < 0.05, respectively, n 75). Moreover, NEFA 16:1 predicted ACS1 expression independently of HOMA, WHR and adipose tissue 16:0 in multiple regression analysis (standardized coefficient = 0.27, P < 0.05). Conclusion: Significant associations were found between measures of insulin sensitivity, adipose tissue FA handling protein expression, and specific FA composition variables. Although causal relationships could not be identified these findings suggest a role of FA handling proteins in relation to insulin sensitivity, via their involvement in FA trafficking and metabolism. In particular they indicate links between ACS1 activity, the distribution of 16:0 and 16:1, and insulin sensitivity, which may be of physiological relevance.
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- Sjögren, P, et al.
(författare)
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Fatty acid desaturases in human adipose tissue : relationships between gene expression, desaturation indexes and insulin resistance
- 2008
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:2, s. 328-335
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Fatty acid desaturases introduce double bonds into growing fatty acid chains. The key desaturases in humans are Delta(5)desaturase (D5D), Delta(6)-desaturase (D6D) and stearoyl-CoA desaturase (SCD). Animal and human data implicate hepatic desaturase activities in insulin resistance, obesity and dyslipidaemia. However, the role of desaturase activity in adipose tissue is uncertain. We therefore evaluated relationships between adipose mRNA expression, estimated desaturase activities (fatty acid ratios) in adipose tissue and insulin resistance. Methods Subcutaneous adipose tissue mRNA expression of D5D (also known as FADS1), D6D (also known as FADS2) and SCD was determined in 75 individuals representative of the study population of 294 healthy 63-year-old men. Desaturation indexes (product/substrate fatty acid ratios) were generated from adipose tissue fatty acid composition in all individuals. Insulin resistance was defined as the upper quartile of the updated homeostasis model assessment (HOMA-2) index. Results The relevant desaturation indexes (16:1/16:0, 18:1/18:0, 20:4/20:3 and 18:3/18:2) reflected expression of SCD, but not of D5D or D6D in adipose tissue. Insulin-resistant individuals had a higher adipose tissue 18:1/18:0, but not 16:1/16:0 ratio than insulin-sensitive individuals. Individuals with a high adipose tissue 18:1/18:0 ratio were 4.4-fold (95% CI 1.8-11.8) more likely to be insulin resistant [threefold (95% CI 1.1-8.6) after adjustment for waist circumference and plasma triacylglycerol]. In a multiple regression model predicting HOMA-2, the independent effect of the 18:1/18:0 ratio was borderline (p=0.086). Conclusions/interpretation Adipose tissue desaturation indexes of SCD reflect the expression of the gene encoding the enzyme in this tissue. Elevated SCD activity within adipose tissue is closely coupled to the development of insulin resistance.
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