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Carboxylesterase 1 gene duplication and mRNA expression in adipose tissue are linked to obesity and metabolic function.

Friedrichsen M, Poulsen P, Wojtaszewski J, Hansen PR, Vaag A, Rasmussen HB - PLoS ONE (2013)

Bottom Line: Furthermore, the heritability of CES1 mRNA expression level in adipose tissue and the effect of CES1 gene duplication were assessed.CES1 gene duplication was positively associated with insulin sensitivity (P = 0.05) as well as glucose tolerance (P = 0.03) and negatively associated with homeostasis model assessment-insulin resistance (P = 0.02).Further studies are needed to understand the potential effect of CES1 gene duplication on adipocyte and whole-body metabolic functions.

View Article: PubMed Central - PubMed

Affiliation: Department of Diabetes and Metabolism, Rigshospitalet, Copenhagen, Denmark.

ABSTRACT

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 CES1 mRNA expression. Here, we investigated CES1 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 CES1 mRNA expression level in adipose tissue and the effect of CES1 gene duplication were assessed.

Methodology: A total of 295 monozygotic and dizygotic twin subjects (62-83 years) with (n = 48) or without (n = 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 CES1 mRNA and copy number of the gene were assessed by quantitative PCR.

Results: 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). The heritability for the expression of CES1 mRNA in adipose tissue was high. CES1 gene duplication was positively associated with insulin sensitivity (P = 0.05) as well as glucose tolerance (P = 0.03) and negatively associated with homeostasis model assessment-insulin resistance (P = 0.02). Duplication of CES1 was not linked to mRNA level of this gene (P = 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 CES1 gene duplication on adipocyte and whole-body metabolic functions.

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CES1 mRNA expression level in adipose tissue in individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), and impaired glucose regulation (IGR = IGT+T2DM). CES1: carboxylesterase 1 gene.*P<0.05 compared to NGT after adjustment for age, gender, and body-mass index.
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pone-0056861-g002: CES1 mRNA expression level in adipose tissue in individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), and impaired glucose regulation (IGR = IGT+T2DM). CES1: carboxylesterase 1 gene.*P<0.05 compared to NGT after adjustment for age, gender, and body-mass index.

Mentions: CES1 and CES1P1 mRNA expression. CES1 mRNA expression level in adipose tissue was significantly affected by age, gender, and BMI (P<0.001 for all variables, Table 1). One year of aging was associated with a decrease in the CES1 mRNA level of 4%, and the expression level in males was 35% lower than in females. Adiposity was associated with a 10% increase in CES1 mRNA level per BMI unit (Table 1 and Figure 1A). Moreover, we found CES1 mRNA level in adipose tissue to be positively associated with HOMA-IR (Table 2 and Figure 1B), where a doubling of this level was associated with a 15% increase in HOMA-IR (P = 0.003). CES1 mRNA level was also positively associated with other measures of metabolic function (Table 2), including cholesterol (P = 0.04), and fasting plasma levels of insulin (P = 0.006), glucose (P = 0.002) and triglycerides (P = 0.003, see also Figure 1C). Conversely, CES1 mRNA level was negatively associated with ISIcomposite (P = 0.005). Finally, there was a positive correlation between the levels of mRNA of CES1 and CES1P1 (Figure 1D). Although CES1 mRNA level was not significantly associated with 120-min OGTT glucose level (Table 2), we found a borderline significant association (P = 0.057) between the levels of OGTT glucose and CES1 mRNA after adjustment for age, sex and BMI (Figure 2). Individuals with IGT and T2DM were combined into one group with impaired glucose regulation. After adjustment for age, sex and BMI the level of CES1 mRNA was 27% higher in the combined group compared with the NGT group (Figure 2).


Carboxylesterase 1 gene duplication and mRNA expression in adipose tissue are linked to obesity and metabolic function.

Friedrichsen M, Poulsen P, Wojtaszewski J, Hansen PR, Vaag A, Rasmussen HB - PLoS ONE (2013)

CES1 mRNA expression level in adipose tissue in individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), and impaired glucose regulation (IGR = IGT+T2DM). CES1: carboxylesterase 1 gene.*P<0.05 compared to NGT after adjustment for age, gender, and body-mass index.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585247&req=5

pone-0056861-g002: CES1 mRNA expression level in adipose tissue in individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), and impaired glucose regulation (IGR = IGT+T2DM). CES1: carboxylesterase 1 gene.*P<0.05 compared to NGT after adjustment for age, gender, and body-mass index.
Mentions: CES1 and CES1P1 mRNA expression. CES1 mRNA expression level in adipose tissue was significantly affected by age, gender, and BMI (P<0.001 for all variables, Table 1). One year of aging was associated with a decrease in the CES1 mRNA level of 4%, and the expression level in males was 35% lower than in females. Adiposity was associated with a 10% increase in CES1 mRNA level per BMI unit (Table 1 and Figure 1A). Moreover, we found CES1 mRNA level in adipose tissue to be positively associated with HOMA-IR (Table 2 and Figure 1B), where a doubling of this level was associated with a 15% increase in HOMA-IR (P = 0.003). CES1 mRNA level was also positively associated with other measures of metabolic function (Table 2), including cholesterol (P = 0.04), and fasting plasma levels of insulin (P = 0.006), glucose (P = 0.002) and triglycerides (P = 0.003, see also Figure 1C). Conversely, CES1 mRNA level was negatively associated with ISIcomposite (P = 0.005). Finally, there was a positive correlation between the levels of mRNA of CES1 and CES1P1 (Figure 1D). Although CES1 mRNA level was not significantly associated with 120-min OGTT glucose level (Table 2), we found a borderline significant association (P = 0.057) between the levels of OGTT glucose and CES1 mRNA after adjustment for age, sex and BMI (Figure 2). Individuals with IGT and T2DM were combined into one group with impaired glucose regulation. After adjustment for age, sex and BMI the level of CES1 mRNA was 27% higher in the combined group compared with the NGT group (Figure 2).

Bottom Line: Furthermore, the heritability of CES1 mRNA expression level in adipose tissue and the effect of CES1 gene duplication were assessed.CES1 gene duplication was positively associated with insulin sensitivity (P = 0.05) as well as glucose tolerance (P = 0.03) and negatively associated with homeostasis model assessment-insulin resistance (P = 0.02).Further studies are needed to understand the potential effect of CES1 gene duplication on adipocyte and whole-body metabolic functions.

View Article: PubMed Central - PubMed

Affiliation: Department of Diabetes and Metabolism, Rigshospitalet, Copenhagen, Denmark.

ABSTRACT

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 CES1 mRNA expression. Here, we investigated CES1 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 CES1 mRNA expression level in adipose tissue and the effect of CES1 gene duplication were assessed.

Methodology: A total of 295 monozygotic and dizygotic twin subjects (62-83 years) with (n = 48) or without (n = 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 CES1 mRNA and copy number of the gene were assessed by quantitative PCR.

Results: 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). The heritability for the expression of CES1 mRNA in adipose tissue was high. CES1 gene duplication was positively associated with insulin sensitivity (P = 0.05) as well as glucose tolerance (P = 0.03) and negatively associated with homeostasis model assessment-insulin resistance (P = 0.02). Duplication of CES1 was not linked to mRNA level of this gene (P = 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 CES1 gene duplication on adipocyte and whole-body metabolic functions.

Show MeSH
Related in: MedlinePlus