| Autor: |
Tuncman, G., Erbay, E., Hom, X., De Vivo, I., Campos, H., Rimm, E. B., Hotamisligil, G. S. |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 5/2/2006, Vol. 103 Issue 18, p6970-6975, 6p, 2 Diagrams, 3 Charts, 2 Graphs |
| Abstrakt: |
Obesity and the associated pathologies including dyslipidemia, insulin resistance, type 2 diabetes, and cardiovascular disease constitute a major threat to global human health. Yet, the genetic factors that differentially predispose individuals to this cluster of pathologies are unclear. The fatty acid-binding protein aP2 is a cytoplasmic lipid chaperon expressed in adipocytes and macrophages. Mice with aP2 deficiency are partially resistant to obesity-induced insulin resistance and type 2 diabetes, have lower circulating triglycerides, and exhibit marked protection against atherosclerosis. Here, we demonstrate a functionally significant genetic variation at the aP2 locus in humans that results in decreased adipose tissue aP2 expression due to alteration of the CAAT box/enhancer-binding protein binding and reduced transcriptional activity of the aP2 promoter. In population genetic studies with 7,899 participants, individuals that carry this T-87C polymorphism had lower serum triglyceride levels and significantly reduced risk for coronary heart disease and type 2 diabetes compared with subjects homozygous for the WT allele. Taken together, our results indicate that reduction in aP2 activity in humans generate a metabolically favorable phenotype that is similar to aP2 deficiency in experimental models. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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