BACKGROUND AND AIMS: The beta(2)-adrenergic receptors are important for adipocyte lipolysis regulation by catecholamines in humans. The beta(2)-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 beta(2)-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 beta(2)-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 beta(1)-, beta(3)- or alpha(2)A-adrenoceptor sensitivity. Heterozygosity at one or several SNPs in the haplotypes influenced the beta(2)-adrenoceptor sensitivity significantly. CONCLUSION: Multiple SNPs in the beta(2)-adrenoceptor gene form several haplotypes that markedly influence beta(2)-receptor function- and catecholamine-induced lipolysis in fat cells. These haplotypes may be important genetic factors behind impaired lipolysis in obesity.
BACKGROUND AND AIMS: The beta(2)-adrenergic receptors are important for adipocyte lipolysis regulation by catecholamines in humans. The beta(2)-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 beta(2)-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 beta(2)-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 beta(1)-, beta(3)- or alpha(2)A-adrenoceptor sensitivity. Heterozygosity at one or several SNPs in the haplotypes influenced the beta(2)-adrenoceptor sensitivity significantly. CONCLUSION: Multiple SNPs in the beta(2)-adrenoceptor gene form several haplotypes that markedly influence beta(2)-receptor function- and catecholamine-induced lipolysis in fat cells. These haplotypes may be important genetic factors behind impaired lipolysis in obesity.
Authors: Magda M Atala; Alessandra Goulart; Grazia M Guerra; Cristiano Mostarda; Bruno Rodrigues; Priscila R Mello; Dulce E Casarine; Maria-Claudia Irigoyen; Alexandre C Pereira; Fernanda M Consolim-Colombo Journal: Am J Transl Res Date: 2015-01-15 Impact factor: 4.060
Authors: Shichun Du; Michael J Joyner; Timothy B Curry; John H Eisenach; Christopher P Johnson; William G Schrage; Michael D Jensen Journal: Physiol Rep Date: 2014-05-20
Authors: Carolina E Hagberg; Qian Li; Maria Kutschke; Debajit Bhowmick; Endre Kiss; Irina G Shabalina; Matthew J Harms; Olga Shilkova; Viviana Kozina; Jan Nedergaard; Jeremie Boucher; Anders Thorell; Kirsty L Spalding Journal: Cell Rep Date: 2018-09-04 Impact factor: 9.423