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Contribution of Genetic and Metabolic Syndrome to Omental Adipose Tissue PAI-1 Gene mRNA and Plasma Levels in Obesity

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Abstract

Background

Plasminogen activator inhibitor type-1 (PAI-1) has already been associated with atherosclerosis; myocardial infarction; and cardiovascular disease risk factors such as obesity, insulin resistance, and dyslipidemia. However, factors regulating PAI-1 adipose tissue (AT) gene expression and plasma levels are not yet well defined.

Aim

This study aims to assess the contribution of PAI-1 omental AT mRNA levels and genetic and metabolic factors to variation in plasma PAI-1 concentrations.

Methods

Ninety-one non-diabetic premenopausal severely obese women (body mass index, BMI >35 kg/m2) undergoing bariatric surgery were phenotyped (fasting plasma glucose, lipid-lipoprotein, and PAI-1 levels) and genotyped for four PAI-1 polymorphisms. Omental AT PAI-1 mRNA levels were determined using real-time polymerase chain reaction. Stepwise regression analysis was used to identify independent PAI-1 AT mRNA and plasma level predictors.

Results

Among the variables included to the stepwise regression analysis, plasma high-density lipoprotein (HDL)-cholesterol (r = 0.38; p = 0.0004) and total cholesterol (r = 0.16; p = 0.0541) levels were the only two (out of 12) independent variables retained as predictive of PAI-1 omental AT mRNA levels, whereas BMI (r = 0.35; p = 0.0039), plasma HDL-cholesterol concentrations (r = −0.31; p = 0.0375), PAI-1 omental AT mRNA levels (r = 0.19; p = 0.0532) and PAI-1-844G/A (p = 0.0023), and rs6092 (p.A15T; p = 0.0358) polymorphisms contributed independently to plasma PAI-1 concentrations. Taken together, these variables explained 17.8% and 31.0% of the variability in PAI-1 AT mRNA and plasma levels, respectively.

Conclusion

These results suggest that PAI-1 polymorphisms contribute significantly to PAI-1 plasma levels but do not support the notion that omental AT is one of its major source.

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Acknowledgments

The morbidly obese cohort was supported, over the years, by the Laval University Merck Frosst/CIHR Research Chair in Obesity. We express our gratitude to Drs. Simon Marceau, Odette Lescelleur, and Simon Biron of the Laval Hospital Surgery Department who sampled AT for this study. We also want to express our gratitude to Yves Gélinas and Michel Lacaille for their technical assistance in AT gene mRNA experiments. Many thanks are also expressed to Drs. Vicky Drapeau and Fanny Therrien for their help in adipose tissue banking management and Dr. Diane Brisson for her thoughtful comments on the manuscript. Dr. Luigi Bouchard is the recipient of a fellowship award from the Heart and Stroke Foundation of Canada (HSFC) and Sanofi-Aventis as well as the Laval University Merck Frosst/CIHR Research Chair in Obesity. Part of this work was supported by the operating grant # MOP-77572 obtained from the Canadian Institutes of Health Research (CIHR). The cooperation of subjects who participated to this study was greatly appreciated.

Conflict of interest disclosure

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Medicine, ECOGENE-21 and Lipid Clinic, Chicoutimi Hospital, Université de Montréal, Saguenay, QC, Canada

    Luigi Bouchard

  2. Lipid Research Centre, CHUQ Research Centre, Université Laval, Quebec, QC, Canada

    Luigi Bouchard, Marie-Claude Vohl, Jean Bergeron & Louis Pérusse

  3. Department of Food Science and Nutrition, Université Laval, Quebec, QC, Canada

    Marie-Claude Vohl

  4. Department of Surgery, Université Laval, Quebec, QC, Canada

    Stéfane Lebel, Frédéric-Simon Hould & Picard Marceau

  5. Department of Social and Preventive Medicine, Université Laval, Quebec, QC, Canada

    Louis Pérusse

  6. Laval Hospital Research Centre, Quebec, QC, Canada

    Pascale Mauriège

  7. Direction de la recherche, Pavillon des Augustines-AUG-5-06, CHAU regional de Chicoutimi, Saguenay, QC, Canada, G1K 7P4

    Luigi Bouchard

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  1. Luigi Bouchard
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  2. Marie-Claude Vohl
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  3. Stéfane Lebel
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  4. Frédéric-Simon Hould
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Correspondence to Luigi Bouchard.

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Bouchard, L., Vohl, MC., Lebel, S. et al. Contribution of Genetic and Metabolic Syndrome to Omental Adipose Tissue PAI-1 Gene mRNA and Plasma Levels in Obesity. OBES SURG 20, 492–499 (2010). https://doi.org/10.1007/s11695-010-0079-1

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  • DOI: https://doi.org/10.1007/s11695-010-0079-1

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