Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation

• Published in: INTERNATIONAL JOURNAL OF OBESITY Vol. 31; no. 5; pp. 813 - 819
• Main Authors: Jocken, J.W.E, Blaak, E.E, Schiffelers, S, Arner, P, Baak, M.A. van, Saris, W.H.M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2007; Nature Publishing; Nature Publishing Group
• Subjects: Adipose Tissue; Adipose Tissue - metabolism; ADRB2 gene; Adrenergic beta-Agonists; Adrenergic beta-Agonists - pharmacology; adrenergic receptors; Adult; alleles; anthropometric measurements; Anthropometry; Arg16 allele; Biological and medical sciences; codons; drug effects; Energy Metabolism; Epidemiology; Fatty acids; Feeding. Feeding behavior; Female; Females; free fatty acids; Fundamental and applied biological sciences. Psychology; gender differences; gene-gender interactions; Genetic aspects; Genetic diversity; genetic polymorphism; genetic techniques and protocols; genetic variance; Genetic Variation; genetics; genotype; Health Promotion and Disease Prevention; Heterotrimeric GTP-Binding Proteins; Heterotrimeric GTP-Binding Proteins - genetics; human genetics; human nutrition; Humans; in vivo studies; Internal Medicine; Isoproterenol; Isoproterenol - pharmacology; lipid peroxidation; Lipolysis; Lipolysis - genetics; Male; Medical sciences; Medicine; Medicine & Public Health; men; Metabolic Diseases; metabolism; nutrition research; Obesity; Obesity - genetics; Obesity - metabolism; original-article; overweight; Oxidation; Oxidation-Reduction; Oxidation-Reduction - drug effects; pharmacology; Physiological aspects; Polymorphism, Single Nucleotide; Polymorphism, Single Nucleotide - genetics; Public Health; Receptors, Adrenergic, beta-2; Receptors, Adrenergic, beta-2 - drug effects; Receptors, Adrenergic, beta-2 - genetics; Risk factors; Single nucleotide polymorphisms; Vertebrates: anatomy and physiology, studies on body, several organs or systems; women; Netherlands; lipolysis; single-nucleotide polymorphism; gene; fat oxidation; Obesity; ADRB2 gene; Genetic variability; Nutrition; Nutrition disorder; Genotype; Metabolic diseases; Lipolysis; β-Adrenergic receptor; Variant; In vivo; GNB3 gene; Association; Gene; Fat; Genetics; Oxidation; Single nucleotide polymorphism; Nutritional status
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/sj.ijo.0803499

Background and aims: Obesity is associated with a blunted β-adrenoceptor-mediated lipolysis and fat oxidation. We investigated whether polymorphisms in codon 16, 27 and 164 of the β (2)-adrenoceptor gene (ADRB2) and exon 10 of the G protein β (3)-subunit gene (GNB3) are associated with alterations in in vivo lipolysis and fat oxidation. Design and methods: Sixty-five male and 43 female overweight and obese subjects (body mass index (BMI) range: 26.1-48.4 kg/m2) were included. Energy expenditure (EE), respiratory quotient (RQ), circulating free fatty acid (FFA) and glycerol levels were determined after stepwise infusion of increasing doses of the non-selective β-agonist isoprenaline (ISO). Results: In women, the Arg16 allele of the ADRB2 gene was associated with a blunted increase in circulating FFA, glycerol and a decreased fat oxidation during ISO stimulation. In men, the Arg16 allele was significantly associated with a blunted increase in FFA but not in glycerol or fat oxidation. Conclusion: These results suggest that genetic variation in the ADRB2 gene is associated with disturbances in in vivo β-adrenoceptor-mediated lipolysis and fat oxidation during β-adrenergic stimulation in overweight and obese subjects; these effects are influenced by gene-gender interactions.