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The hormone-sensitive lipase C–60G promoter polymorphism is associated with increased waist circumference in normal-weight subjects

International Journal of Obesity volume 30, pages 1442–1448 (2006)Cite this article

Abstract

Objective:

Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of fatty acids from triglyceride stores in adipocytes. The aim of the present study was to investigate the role of the HSL gene promoter variant C-60G, a polymorphism which previously has been associated with reduced promoter activity in vitro, in obesity and type 2 diabetes.

Design:

We genotyped two materials consisting of obese subjects and non-obese controls, one material with offspring-parents trios, where the offspring was abdominally obese and one material with trios, where the offspring had type 2 diabetes or impaired glucose homeostasis. HSL promoter containing the HSL C-60G G-allele was generated and tested against a construct with the C-allele in HeLa cells and primary rat adipocytes. HSL mRNA levels were quantified in subcutaneous and visceral fat from 33 obese subjects.

Results:

We found that the common C-allele was associated with increased waist circumference and WHR in lean controls, but there was no difference in genotype frequency between obese and non-obese subjects. There was a significant increased transmission of C-alleles to the abdominally obese offspring but no increased transmission of C-alleles was observed to offspring with impaired glucose homeostasis. The G-allele showed reduced transcription in HeLa cells and primary rat adipocytes. HSL mRNA levels were significantly higher in subcutaneous compared to visceral fat from obese subjects.

Conclusion:

The HSL C-60G polymorphism is associated with increased waist circumference in non-obese subjects.

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Acknowledgements

This investigation was funded by the Crafoord Foundation, Malmö University Hospital Foundation, the Albert Påhlsson Foundation, the Swedish Research Council, the Diabetes Association in Malmö, the Juvenile Diabetes-Wallenberg Foundation, the Lundberg Foundation, EC-GIFT, the Novo Nordisk Foundation, Region Skåne, ALF, the Magnus Bergvall Foundation, the Fredrik and Ingrid Thurings Foundation and the Borgströms Foundation. We are greatly indebted to the study subjects for their participation. We thank Drs. Henrik Laurell and Dominique Langin, INSERM, Toulouse, for the kind gift of the pGL3-HSL plasmid.

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Authors and Affiliations

  1. Department of Clinical Sciences, Diabetes and Endocrinology, Malmö University Hospital, Lund University, Sweden

    E Carlsson, L E Johansson, L Groop & M Ridderstråle

  2. Division of Diabetes, Metabolism and Endocrinology, Lund University, Lund, Sweden

    K Ström & C Holm

  3. Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden

    J Hoffstedt

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  1. E Carlsson
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  2. L E Johansson
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Correspondence to E Carlsson.

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Carlsson, E., Johansson, L., Ström, K. et al. The hormone-sensitive lipase C–60G promoter polymorphism is associated with increased waist circumference in normal-weight subjects. Int J Obes 30, 1442–1448 (2006). https://doi.org/10.1038/sj.ijo.0803299

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