Cerebral serotonin transporter binding is inversely related to body mass index.
Overweight and obesity is a health threat of increasing concern and understanding the neurobiology behind obesity is instrumental to the development of effective treatment regimes. Serotonergic neurotransmission is critically involved in eating behaviour; cerebral level of serotonin (5-HT) in animal models is inversely related to food intake and body weight and some effective anti-obesity agents involve blockade of the serotonin transporter (SERT). We investigated in 60 healthy volunteers body mass index (BMI) and regional cerebral SERT binding as measured with [(11)C]DASB PET. In a linear regression model with adjustment for relevant covariates, we found that cortical and subcortical SERT binding was negatively correlated to BMI (-0.003 to -0.012 BP(ND) unit per kg/m(2)). Tobacco smoking and alcohol consumption did not affect cerebral SERT binding. Several effective anti-obesity drugs encompass blockade of the SERT; yet, our study is the first to demonstrate an abnormally decreased cerebral SERT binding in obese individuals. Whether the SERT has a direct role in the regulation of appetite and eating behaviour or whether the finding is due to a compensatory downregulation of SERT secondary to other dysfunction(s) in the serotonergic transmitter system, such as low baseline serotonin levels, remains to be established.
Erritzoe
D
D
Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. david@nru.dk
Frokjaer
V G
VG
Haahr
M T
MT
Kalbitzer
J
J
Svarer
C
C
Holst
K K
KK
Hansen
D L
DL
Jernigan
T L
TL
Lehel
S
S
Knudsen
G M
GM
D000328:Adult; D000428:Alcohol Drinking / Q000378:metabolism; D001596:Benzylamines; D015992:Body Mass Index; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D010775:Photic Stimulation; D049268:Positron-Emission Tomography; D015800:Protozoan Proteins; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D012727:Sex Characteristics; D012815:Signal Processing, Computer-Assisted; D012907:Smoking / Q000378:metabolism
D001596:Benzylamines; D002250:Carbon Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D015800:Protozoan Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C072098:aginactin protein, Dictyostelium