Beta2-adrenoceptor polymorphisms relate to obesity through blunted leptin-mediated sympathetic activation.
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.
Masuo
Kazuko
K
Human Neurotransmitter Laboratory, Baker Heart Research Institute, Melbourne, Victoria, Australia. kmasuo@baker.edu.au
Katsuya
Tomohiro
T
Kawaguchi
Hideki
H
Fu
Yuxiao
Y
Rakugi
Hiromi
H
Ogihara
Toshio
T
Tuck
Michael L
ML
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*
C515448:LEPR protein, human; D020738:Leptin; D018343:Receptors, Adrenergic, beta-2; D054411:Receptors, Leptin; D018698:Glutamic Acid; D005998:Glycine; D009638:Norepinephrine