Carboxylesterase 1 Gene Duplication and mRNA Expression in Adipose Tissue Are Linked to Obesity and Metabolic Function

Friedrichsen, Martin; Poulsen, Pernille; Wojtaszewski, Jørgen; Hansen, Peter Riis; Vaag, Allan; Rasmussen, Henrik Berg
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
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.


Related Articles

  • Serum amyloid A: production by human white adipocyte and regulation by obesity and nutrition. Poitou, C.; Viguerie, N.; de Cancello, R.; de Matteis, R.; Cinti, S.; Stich, V.; Coussieu, C.; Gauthier, E.; Courtine, M.; Zucker, J. D.; Barsh, G. S.; Saris, W.; Bruneval, P.; Basdevant, A.; Langin, D.; Clément, K. // Diabetologia;Mar2005, Vol. 48 Issue 3, p519 

    Aims/hypothesis: The acute-phase proteins, serum amyloid As (SAA), are precursors of amyloid A, involved in the pathogenesis of AA amyloidosis. This work started with the characterisation of systemic AA amyloidosis concurrent with SAA overexpression in the subcutaneous white adipose tissue...

  • Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression. Boucher, J.; Quilliot, D.; Pradères, J. P.; Simon, M. F.; Grès, S.; Guigné, C.; Prévot, D.; Ferry, G.; Boutin, J. A.; Carpéné, C.; Valet, P.; Saulnier-Blache, J. S. // Diabetologia;Mar2005, Vol. 48 Issue 3, p569 

    Aims/hypothesis: Autotaxin is a lysophospholipase D that is secreted by adipocytes and whose expression is substantially up-regulated in obese, diabetic db/db mice. The aim of the present study was to depict the physiopathological and cellular mechanisms involved in regulation of adipocyte...

  • Correlation of Peroxisome Proliferator-Activated Receptor ( PPAR-γ) mRNA Expression with Pro12Ala Polymorphism in Obesity. Berhouma, Rym; Kouidhi, Soumaya; Ammar, Myriam; Abid, Hafawa; Ennafaa, Hajer; Benammar-Elgaaied, Amel // Biochemical Genetics;Apr2013, Vol. 51 Issue 3/4, p256 

    Our study aimed to analyze whether the expression of PPARγ mRNA in subcutaneous adipocyte tissue correlates with Pro12Ala PPARγ2 polymorphism in the obesity context. We found that mRNA expression of PPARγ in subcutaneous adipose tissue was greater in obese subjects ( P < 0.05) than in...

  • Regulation of Adiponutrin Expression in Subcutaneous Adipose Tissue of Humans. Considine, Robert V.; Bell, Lauren N.; Fulford, Angle D.; Shankar, Sodha S.; Steinberg, Helmut O. // Diabetes;Jun2007 Supplement 1, Vol. 56, pA358 

    Dysregulation of fatty acid storage and release by adipose tissue contributes to the pathophysiology of insulin resistance and diabetes. Adiponutrin is a newly discovered enzyme involved in triglyceride metabolism in adipose tissue. To elucidate the regulation of adiponutrin gene expression, we...

  • Human growth hormone receptor (GHR) expression in obesity: I. GHR mRNA expression in omental and subcutaneous adipose tissues of obese women. Erman, A; Veilleux, A; Tchernof, A; Goodyer, C G // International Journal of Obesity;Dec2011, Vol. 35 Issue 12, p1511 

    Objectives:Growth hormone (GH)-deficient individuals display increased adiposity that can be effectively reduced by GH therapy because of GH's lipolytic effects. However, similar GH treatments of individuals with idiopathic obesity (not associated with an endocrinopathy/syndrome) have had little...

  • Fibronectin Gene Expression in Human Adipose Tissue and Its Associations with Obesity-Related Genes and Metabolic Parameters. Lee, Seoung; Park, Hye; Lee, Jung; Song, Young; Jang, Yeon; Kim, Jong-Hyeok; Lee, Yeon; Heo, Yoonseok // Obesity Surgery;Apr2013, Vol. 23 Issue 4, p554 

    Background: Limited data are available on the in vivo expression of fibronectin, one of the main extracellular matrix components. We investigated the expression of fibronectin in abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and the associations of leptin,...

  • Expression of Inflammation-Related Genes in Gluteal and Abdominal Subcutaneous Adipose Tissue During Weight-Reducing Dietary Intervention in Obese Women. MALIŠOVÁ, L.; ROSSMEISLOVÁ, L.; KOVÁČOVÁ, Z.; KRAČMEROVÁ, J.; TENCEROVÁ, M.; LANGIN, D.; ŠIKLOVÁ-VÍTKOVÁ, M.; ŠTICH, V. // Physiological Research;2014, Vol. 63 Issue 1, p73 

    Accumulation of adipose tissue in lower body lowers risk of cardiovascular and metabolic disorders. The molecular basis of this protective effect of gluteofemoral depot is not clear. The aim of this study was to compare the profile of expression of inflammation-related genes in subcutaneous...

  • Gene Profiling of Human Adipose Tissue During Evoked Inflammation In Vivo. Shah, Rachana; Lu, Yun; Hinkle, Christine C.; McGillicuddy, Fiona C.; Kim, Roy; Hannenhalli, Sridhar; Cappola, Thomas P.; Heffron, Sean; Wang, XingMei; Mehta, Nehal N.; Putt, Mary; Reilly, Muredach P. // Diabetes;Oct2009, Vol. 58 Issue 10, p2211 

    OBJECTIVE--Adipose inflammation plays a central role in obesity-related metabolic and cardiovascular complications. However, few human adipose-secreted proteins are known to mediate these processes. We hypothesized that microarray mRNA profiling of human adipose during evoked inflammation could...

  • Coadministration of Coenzyme Q prevents Rosiglitazone-induced adipogenesis in ob/ob mice. Carmona, M. C.; Lefebvre, P.; Lefebvre, B.; Galinier, A.; Benani, A.; Jeanson, Y.; Louche, K.; Flajollet, S.; Ktorza, A.; Dacquet, C.; Pénicaud, L.; Casteilla, L. // International Journal of Obesity;Feb2009, Vol. 33 Issue 2, p204 

    Objective:The aim of this study is to determine the effect of coenzyme Q (Q) on ob/ob mice treated or not with thiazolidinedione (TZD).Design and measurements:Ob/ob mice were treated with Q, Rosiglitazone or a combination of both molecules for 13 days; physical and metabolic parameters as well...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics