Central 5-HT neurotransmission modulates weight loss following gastric bypass surgery in obese individuals

Abstract

The cerebral serotonin (5-HT) system shows distinct differences in obesity compared with the lean state. Here, it was investigated whether serotonergic neurotransmission in obesity is a stable trait or changes in association with weight loss induced by Roux-in-Y gastric bypass (RYGB) surgery. In vivo cerebral 5-HT2A receptor and 5-HT transporter binding was determined by positron emission tomography in 21 obese [four men; body mass index (BMI), 40.1 ± 4.1 kg/m(2)] and 10 lean (three men; BMI, 24.6 ± 1.5 kg/m(2)) individuals. Fourteen obese individuals were re-examined after RYGB surgery. First, it was confirmed that obese individuals have higher cerebral 5-HT2A receptor binding than lean individuals. Importantly, we found that higher presurgical 5-HT2A receptor binding predicted greater weight loss after RYGB and that the change in 5-HT2A receptor and 5-HT transporter binding correlated with weight loss after RYGB. The changes in the 5-HT neurotransmission before and after RYGB are in accordance with a model wherein the cerebral extracellular 5-HT level modulates the regulation of body weight. Our findings support that the cerebral 5-HT system contributes both to establish the obese condition and to regulate the body weight in response to RYGB.

Keywords: 5-HT; 5-HT transporter; 5-HT2A receptor; bariatric surgery; positron emission tomography.

Figure 1.

The estimated correlation (with 95% confidence intervals) between neocortical 5-HT_2AR binding (BP_P) before RYGB and weight loss after RYGB. ΔBMI = BMI_pre − BMI_post.

Figure 2.

Neocortical 5-HT_2AR binding (BP_P) in pre-RYGB, post-RYGB, and lean individuals. Bars show the mean and SDs for the three groups.

Figure 3.

Differences in mean 5-HT_2AR binding across neocortex in obese (left) and healthy (right) individuals. The color bar represents binding potential (BP_P). The image was generated using parametric maps generated using PXMOD and normalized into Montreal Neurological Institute (MNI) space using SPM8 (failed for two obese individuals whose data were not included). After smoothing mean BP_P, maps were computed for each group and projected onto a T1 image in MNI space using a software package developed at the Neurobiology Research Unit, Rigshospitalet.

Figure 4.

RYGB induced change in BMI versus change in binding potential for cerebral 5-HT_2AR and 5-HTT in individuals with both [¹¹C]DASB PET and [¹⁸F]altanserin PET rescans (dashed line, 5-HT_2AR BP_P; solid line, 5-HTT BP_ND). Each symbol indicates the 5-HT_2A and 5-HTT levels in the individual persons. The open triangle represents the 5-HT_2AR and the 5-HTT change in one single individual associated with the change in BMI in that same individual; % change in BP is the percentage change in the specific radiotracer binding defined as [(BP_post/BP_pre) − 1) × 100]; and ΔBMI is the BMI after surgery subtracted by the BMI before surgery.

Figure 5.

The solid line represents the estimated quadratic relationship between neocortical 5-HT_2AR-specific radiotracer binding (BP_P) and subcortical (caudate, putamen, and thalamus) 5-HTT-specific radiotracer binding (BP_ND). The 95% confidence interval is represented by the thin lines. Black dots, Pre-RYGB participants; crosses, lean participants; open triangles, post-RYGB participants.