Abstract
Context and aimsCarboxylesterase 1 (CES1) plays an important role in the control of the metabolism of triglycerides and cholesterol in various cell types including adipocytes and hepatocytes. In this study we investigated CES1 mRNA expression in adipose tissue as well as CES1 gene duplication and their association with measures of adiposity and metabolic function in a large twin population.Methodology295 monozygotic and dizygotic twins (62–83 years) were subjected to a standard OGTT and excision of abdominal subcutaneous fat biopsies. Levels of CES1 mRNA and DNA copy number of the CES1 gene were assessed by quantitative PCR.ResultsCES1 mRNA expression in adipose tissue was positively associated with BMI (P<0.001), insulin resistance ([HOMA], P=0.003) and fasting levels of glucose (P=0.002), insulin (P=0.006), and triglycerides (P=0.003). Gene duplication of CES1 was not linked to altered CES1 mRNA expression (P=0.63). Nonetheless, CES1 gene duplication was associated with increased glucose tolerance (P=0.03) and decreased insulin resistance (P=0.02).ConclusionCES1 mRNA expression in adipocytes as well as CES1 gene duplication were associated with measures of glucose metabolism, which raises the possibility of a potential role for this enzyme in the development of type 2 diabetes.
Highlights
Adipose tissue is the major site for storage of cholesterol and triglycerides in the body [1,2] The hydrolysis and esterification of lipids in this tissue are closely regulated to maintain a tight balance between lipid release, storage, and trafficking [3]
Carboxylesterase 1 (CES1) mRNA expression level in adipose tissue was positively associated with body-mass index (P,0.001), homeostasis model assessment-insulin resistance (P = 0.003) and level of fasting glucose (P = 0.002), insulin (P = 0.006), and triglycerides (P = 0.003)
Further studies are needed to understand the potential effect of CES1 gene duplication on adipocyte and whole-body metabolic functions
Summary
Adipose tissue is the major site for storage of cholesterol and triglycerides in the body [1,2] The hydrolysis and esterification of lipids in this tissue are closely regulated to maintain a tight balance between lipid release, storage, and trafficking [3]. Disturbance of this balance may lead to insulin resistance, increased plasma levels of triglycerides, and obesity, i.e. components of the metabolic syndrome [3]. Several enzymes are implicated in the lipid metabolism in human adipose tissue [4] This includes carboxylesterase 1 (CES1) that seems to play an important role in the hydrolysis of cholesteryl esters and triglycerides [5]. The enzyme appears to be involved in the de-esterification as well as transesterification of lipids
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