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

J Neurosci. 2015 Apr 8;35(14):5884-9. doi: 10.1523/JNEUROSCI.3348-14.2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Brain / diagnostic imaging
  • Brain / pathology*
  • Brain Mapping
  • Case-Control Studies
  • Denmark
  • Female
  • Gastric Bypass / methods*
  • Glucagon-Like Peptide 1 / blood
  • Humans
  • Ketanserin / analogs & derivatives
  • Ketanserin / pharmacokinetics
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / diagnostic imaging
  • Obesity / surgery*
  • Protein Binding / drug effects
  • Radionuclide Imaging
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Serotonin Antagonists / pharmacokinetics
  • Time Factors
  • Treatment Outcome
  • Weight Loss / physiology*

Substances

  • Receptor, Serotonin, 5-HT2A
  • Serotonin Antagonists
  • altanserin
  • Glucagon-Like Peptide 1
  • Ketanserin