Influence of sex and beta2 adrenergic receptor haplotype on resting and terbutaline-stimulated whole body lipolysis.
beta 2 adrenergic receptors ( beta 2 ARs) are important mediators of lipolysis. The beta 2 AR gene is highly polymorphic. To determine the contribution of beta 2 AR polymorphisms to variability in whole body lipolysis, we compared basal and terbutaline-stimulated lipolytic rates (Ra) using tracer techniques in 14 healthy, non-obese males (n=7) and females (n=7) who were homozygous for Cys-19/Arg16/Gln27 or Arg-19/Gly16/Glu27 haplotypes. Fasting (overnight) Ra values were higher in females compared to males. Mean+/-SD Ra, Ra/body weight, Ra/fat free mass, Ra/fat, and Ra/energy expenditure rates in males and females were 155+/-46 vs 311+/-111 micromol/min (P=.007); 2.0+/-0.61 vs 5.2+/-2.3 micromol/(min kg) (P=.006); 2.5+/-0.75 vs 7.8+/-3.4 micromol/(min kg) (P=.003); 10+/-3.7 vs 17+/-7.4 micromol/(min kg) (P=.09); and 144+/-45.5 vs 392+/-111 micromol/d (P=.0001), respectively. Mean+/-SD basal glycerol concentrations were higher in females compared to males: 62+/-5.6 vs 36+/-17 micromol/L (P=.003). Basal glycerol concentrations and Ra values were similar by beta2 AR haplotype. Basal glucose and insulin concentrations tended to be higher in males compared to females and were similar by haplotype. Terbutaline-stimulated changes in glycerol concentrations were variable and are not related to either sex or haplotype. We conclude that compared to haplotype, sex is a more important determinant of basal lipolysis after a 12-hour fast in healthy, non-obese individuals.
Lima
John J
JJ
Centers for Clinical Pediatric Pharmacology and Pharmacogenetics, Nemours Children's Clinic, Jacksonville, FL 32207, USA. jlima@nemours.org
Mauras
Nelly
N
Kissoon
Niranjan
N
Wang
Jianwei
J
Wiltrout
Stacey Armatti
SA
Sylvester
James E
JE
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D004734:Energy Metabolism; D005260:Female; D005990:Glycerol / Q000097:blood; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000097:blood; D007700:Kinetics; D015227:Lipid Peroxidation; D008066:Lipolysis / Q000187:drug effects / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012016:Reference Values; D012727:Sex Characteristics; D013726:Terbutaline / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D007328:Insulin; D018343:Receptors, Adrenergic, beta-2; D013726:Terbutaline; D005990:Glycerol