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Relationship between β-2 adrenoceptor gene haplotypes and adipocyte lipolysis in women

International Journal of Obesity volume 28, pages 185–190 (2004)Cite this article

Abstract

BACKGROUND AND AIMS: The β2-adrenergic receptors are important for adipocyte lipolysis regulation by catecholamines in humans. The β2-adrenoceptor gene is highly polymorphic. The role of these genetic variations for adipocyte lipolysis was investigated.

DESIGN AND METHODS: Six single-nucleotide polymorphisms (SNPs) in the promotor region and four SNPs in the coding region (leading to amino-acid substitution) of the β2-adrenoceptor gene were determined in 141 overweight or obese, but otherwise healthy women. Lipolysis experiments were performed on isolated subcutaneous adipocytes.

RESULTS: Three homozygous haplotypes (6/6, 4/4 and 2/2) were found that differed about 500-fold in noradrenaline sensitivity or β2-adrenoceptor sensitivity (6/6>2/2>4/4, P=0.01). The haplotypes also differed by 100% in maximum noradrenaline-induced lipolysis rates (6/6>2/2>4/4). However, there was no influence on β1-, β3- or α2A-adrenoceptor sensitivity. Heterozygosity at one or several SNPs in the haplotypes influenced the β2-adrenoceptor sensitivity significantly.

CONCLUSION: Multiple SNPs in the β2-adrenoceptor gene form several haplotypes that markedly influence β2-receptor function- and catecholamine-induced lipolysis in fat cells. These haplotypes may be important genetic factors behind impaired lipolysis in obesity.

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Acknowledgements

We are indebted to Eva Sjölin, Britt-Marie Leijonhufvud, Katarina Hertel, Kerstin Wåhlén and Elisabeth Dungner for skilful assistance. This work was supported by grants from Swedish Research Coundil, Swedish Diabetes Association, Novo Nordic Foundation, Söderberg Foundation, Swedish Heart and Lung Foundation, the King Gustaf V and Queen Victorias Foundation and the Foundation for Old Servants, Thuring and Wiberg and the Swedish Society of Medicine.

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  1. Gustaf V Research Institute, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden

    P Eriksson

  2. Department of Medicine, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden

    I Dahlman, M Rydén, J Hoffstedt & P Arner

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  1. P Eriksson
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Correspondence to P Arner.

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Eriksson, P., Dahlman, I., Rydén, M. et al. Relationship between β-2 adrenoceptor gene haplotypes and adipocyte lipolysis in women. Int J Obes 28, 185–190 (2004). https://doi.org/10.1038/sj.ijo.0802521

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