Serotonin Transporter Binding in the Diencephalon Is Reduced in Insulin-Resistant Obese Humans.
BACKGROUND
Altered brain dopaminergic and serotonergic pathways have been shown in obese rodents and humans, but it is unknown whether this is related to obesity per se or to the metabolic derangements associated with obesity.


METHODS
We performed a case-control study in insulin-sensitive obese (ISO) and insulin-resistant obese (IRO) subjects (n = 12) and age-matched lean controls (n = 8) and measured serotonin transporter (SERT) binding in the whole diencephalon and specifically in the hypothalamus, as well as dopamine transporter (DAT) binding in the striatum using 123I- FP-CIT single-photon emission computed tomography. We assessed insulin sensitivity using the homeostatic model assessment of insulin resistance.


RESULTS
BMI did not differ between the IRO and ISO subjects. SERT binding in the diencephalon was significantly lower in IRO than in ISO subjects, but was not different between lean and obese subjects. SERT binding in the hypothalamus tended to be reduced in obese versus lean subjects, but was not different between IRO and ISO subjects. Striatal DAT binding was similar between lean and obese subjects as well as between ISO and IRO subjects.


CONCLUSIONS
We conclude that SERT binding in the diencephalon is reduced in insulin-resistant subjects independently of body weight, while hypothalamic SERT binding tends to be lower in obesity, with no difference between insulin-resistant and insulin-sensitive subjects. This suggests that the metabolic perturbations associated with obesity independently affect SERT binding within the diencephalon.
Department of Endocrinology and Metabolism, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Ruth I
RI
Versteeg
Karin E
KE
Koopman
Jan
J
Booij
Mariëtte T
MT
Ackermans
Unga A
UA
Unmehopa
Eric
E
Fliers
Susanne E
SE
la Fleur
Mireille J
MJ
Serlie
D000328:Adult; D015992:Body Mass Index; D001931:Brain Mapping; D016022:Case-Control Studies; D004027:Diencephalon / Q000000981:diagnostic imaging / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009765:Obesity / Q000000981:diagnostic imaging / Q000378:metabolism*; D011485:Protein Binding; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes
D050483:Dopamine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
Dopamine transporter; Human imaging; Insulin resistance; Obesity; Serotonin transporter