Cerebral serotonin transporter binding is inversely related to body mass index

TY - JOUR

T1 - Cerebral serotonin transporter binding is inversely related to body mass index

AU - Erritzoe, D

AU - Frokjaer, V G

AU - Haahr, M T

AU - Kalbitzer, J

AU - Svarer, C

AU - Holst, K K

AU - Hansen, D L

AU - Jernigan, T L

AU - Lehel, S

AU - Knudsen, G M

N1 - Copyright 2010 Elsevier Inc. All rights reserved.

PY - 2010/8/1

Y1 - 2010/8/1

N2 - 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.

AB - 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.

KW - Adult

KW - Alcohol Drinking

KW - Benzylamines

KW - Body Mass Index

KW - Brain

KW - Carbon Radioisotopes

KW - Female

KW - Humans

KW - Linear Models

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Obesity

KW - Photic Stimulation

KW - Positron-Emission Tomography

KW - Protozoan Proteins

KW - Serotonin Plasma Membrane Transport Proteins

KW - Sex Characteristics

KW - Signal Processing, Computer-Assisted

KW - Smoking

U2 - 10.1016/j.neuroimage.2010.03.086

DO - 10.1016/j.neuroimage.2010.03.086

M3 - Journal article

C2 - 20382236

SN - 1053-8119

VL - 52

SP - 284

EP - 289

JO - NeuroImage

JF - NeuroImage

IS - 1

ER -