Friedrichsen_2013_PLoS.One_8_e56861

CONTEXT AND AIMS: Carboxylesterase 1 (CES1) appears to play an important role in the control of the metabolism of triglycerides and cholesterol in adipocytes and other cell types including hepatocytes. Therefore, it is relevant to gain insights into the genetic versus non-genetic mechanisms involved in the control of mRNA expression. Here, we investigated mRNA expression level in adipose tissue and its association with measures of adiposity and metabolic function in a population of elderly twins. Furthermore, the heritability of mRNA expression level in adipose tissue and the effect of gene duplication were assessed. METHODOLOGY: A total of 295 monozygotic and dizygotic twin subjects (62-83 years) with ( = 48) or without ( = 247) type 2 diabetes mellitus were enrolled in the study. They were subjected to a standard oral glucose tolerance test and excision of abdominal subcutaneous fat biopsies during the fasting state. Levels of mRNA and copy number of the gene were assessed by quantitative PCR.
RESULTS: mRNA expression level in adipose tissue was positively associated with body-mass index (<0.001), homeostasis model assessment-insulin resistance ( = 0.003) and level of fasting glucose ( = 0.002), insulin ( = 0.006), and triglycerides ( = 0.003). The heritability for the expression of mRNA in adipose tissue was high. gene duplication was positively associated with insulin sensitivity ( = 0.05) as well as glucose tolerance ( = 0.03) and negatively associated with homeostasis model assessment-insulin resistance ( = 0.02). Duplication of was not linked to mRNA level of this gene ( = 0.63). CONCLUSION: CES1 mRNA in adipose tissue appears to be under strong genetic control and was associated with measures of metabolic function raising the possibility of a potential role of this enzyme in the development of type 2 diabetes mellitus. Further studies are needed to understand the potential effect of gene duplication on adipocyte and whole-body metabolic functions.