Serotonin Transporter Binding in the Diencephalon Is Reduced in Insulin-Resistant Obese Humans.

Abstract

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.

• Authors: Ruth I Versteeg, Karin E Koopman, Jan Booij, Mariëtte T Ackermans, Unga A Unmehopa, Eric Fliers, Susanne E la Fleur, Mireille J Serlie
• Journal: Neuroendocrinology (Neuroendocrinology) Vol. 105 Issue 2 Pg. 141-149 ( 2017) ISSN: 1423-0194 [Electronic] Switzerland
• PMID: 27626923 (Publication Type: Journal Article)
• Copyright: © 2016 The Author(s) Published by S. Karger AG, Basel.

Chemical References

• Dopamine Plasma Membrane Transport Proteins
• Radiopharmaceuticals
• SLC6A4 protein, human
• Serotonin Plasma Membrane Transport Proteins
• Tropanes
• 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane

Topics

• Adult
• Body Mass Index
• Brain Mapping
• Case-Control Studies
• Diencephalon (diagnostic imaging, metabolism)
• Dopamine Plasma Membrane Transport Proteins (metabolism)
• Female
• Humans
• Insulin Resistance (physiology)
• Magnetic Resonance Imaging
• Male
• Obesity (diagnostic imaging, metabolism)
• Protein Binding
• Radiopharmaceuticals
• Serotonin Plasma Membrane Transport Proteins (metabolism)
• Tomography, Emission-Computed, Single-Photon
• Tropanes