title: Beta2-adrenoceptor polymorphisms relate to obesity through blunted leptin-mediated sympathetic activation.
abstract: BACKGROUND
  Obesity is a growing public health problem. It has been reported that beta2-adrenoceptor polymorphisms are associated with obesity. This study examines the associations of beta2-adrenoceptor polymorphism with relationships between plasma norepinephrine (NE) and leptin to evaluate further the mechanisms of obesity.
  
  
  METHODS
  In 329 normotensive (BP <140/90 mm Hg) men with a wide range of BMI (17.0 to 36.5 kg/m2), we measured BMI, total body fat mass, waist-to-hip ratio (W/H), BP, plasma NE, leptin, and the beta2-(Arg16Gly, Gln27Glu) adrenoceptor polymorphisms. The subjects consisted of 206 nonobese (BMI <25 kg/m2) and 123 overweight or obese (BMI >or=25 kg/m2) men.
  
  
  RESULTS
  Overweight or obese subjects had a significantly higher frequency of Gly16 and Glu27 alleles compared with nonobese subjects. The subjects carrying Gly16 or Glu27 alleles regardless of BMI had greater total fat mass, W/H and plasma leptin compared with those without the Gly16 or Glu27 alleles, indicating that Gly16 and Glu27 alleles of the beta2-adrenoceptor gene are related to obesity and fat mass. Only in the nonobese subjects who carried the Gly16 and Glu27 alleles was there a high plasma NE level, but similar in overweight or obese subjects. To evaluate leptin-mediated sympathetic activation, we performed linear regression analyses between plasma leptin and NE. In groups with and without the Gly16 or Glu27 alleles, plasma leptin correlated with NE, but the slope in the group carrying the Gly16 or Glu27 allele was significantly lower than that without the Gly16 or Glu27.
  
  
  CONCLUSIONS
  The findings demonstrate a strong and significant association of the Gly16 and Glu27 alleles with obesity. Lower slopes between leptin and NE in the subjects carrying these beta2-adrenoceptor polymorphisms indirectly indicate a blunted leptin-mediated sympathetic nerve activity. We propose that the beta2-adrenoceptor polymorphisms related to blunted leptin-mediated sympathetic activation offers further proof for the mechanisms of obesity.
authors.affiliation: Human Neurotransmitter Laboratory, Baker Heart Research Institute, Melbourne, Victoria, Australia. kmasuo@baker.edu.au
authors.forename: Kazuko
authors.initials: K
authors.lastname: Masuo
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.forename: Hideki
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Yuxiao
authors.initials: Y
authors.lastname: Fu
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Michael L
authors.initials: ML
authors.lastname: Tuck
mesh_terms: D000328:Adult; D000483:Alleles; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D015331:Cohort Studies; D005786:Gene Expression Regulation / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics / Q000502:physiology; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism; D005998:Glycine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000097:blood / Q000235:genetics / Q000502:physiology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood / Q000235:genetics / Q000502:physiology; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000502:physiology*; D054411:Receptors, Leptin; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: C515448:LEPR protein, human; D020738:Leptin; D018343:Receptors, Adrenergic, beta-2; D054411:Receptors, Leptin; D018698:Glutamic Acid; D005998:Glycine; D009638:Norepinephrine