title: Cerebral serotonin transporter binding is inversely related to body mass index.
abstract: 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.
authors.affiliation: Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. david@nru.dk
authors.forename: D
authors.initials: D
authors.lastname: Erritzoe
authors.forename: V G
authors.initials: VG
authors.lastname: Frokjaer
authors.forename: M T
authors.initials: MT
authors.lastname: Haahr
authors.forename: J
authors.initials: J
authors.lastname: Kalbitzer
authors.forename: C
authors.initials: C
authors.lastname: Svarer
authors.forename: K K
authors.initials: KK
authors.lastname: Holst
authors.forename: D L
authors.initials: DL
authors.lastname: Hansen
authors.forename: T L
authors.initials: TL
authors.lastname: Jernigan
authors.forename: S
authors.initials: S
authors.lastname: Lehel
authors.forename: G M
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: 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
chemical_list: 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