5-Hydroxytryptamine Medications for the Treatment of Obesity

Luke K. Burke, Lora Heisler

Research output: Contribution to journalLiterature review

28 Citations (Scopus)

Abstract

The central 5-hydroxytryptamine (5-HT; serotonin) system represents a fundamental component of the brain's control of energy homeostasis. Medications targeting the 5-HT pathway have been at the forefront of obesity treatment for the past 15years. Pharmacological agents targeting 5-HT receptors (5-HTR), in combination with genetic models of 5-HTR manipulation, have uncovered a role for specific 5-HTRs in energy balance and reveal the 5-HT2CR as the principal 5-HTR mediating this homeostatic process. Capitalising on this neurophysiological machinery, 5-HT2CR agonists improve obesity and glycaemic control in patient populations. The underlying therapeutic mechanism has been probed using model systems and appears to be achieved primarily through 5-HT2CR modulation of the brain melanocortin circuit via activation of pro-opiomelanocortin neurones signalling at melanocortin4 receptors. Thus, 5-HT2CR agonists offer a means to improve obesity and type 2 diabetes, which are conditions that now represent global challenges to human health.

Original languageEnglish
Pages (from-to)389-398
Number of pages10
JournalJournal of Neuroendocrinology
Volume27
Issue number6
Early online date26 May 2015
DOIs
Publication statusPublished - Jun 2015

Keywords

  • serotonin
  • 5-HT2CR
  • obesity
  • type 2 diabetes
  • lorcaserin
  • neurons regulate energy
  • receptor knockout mice
  • central-nervous-system
  • behavioral satiety sequence
  • type-2 diabetes-mellitus
  • blood-glucose control
  • food-intake
  • 5-HT1B receptor
  • D-fenfluramine
  • weight-loss

Cite this

5-Hydroxytryptamine Medications for the Treatment of Obesity. / Burke, Luke K.; Heisler, Lora.

In: Journal of Neuroendocrinology, Vol. 27, No. 6, 06.2015, p. 389-398.

Research output: Contribution to journalLiterature review

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abstract = "The central 5-hydroxytryptamine (5-HT; serotonin) system represents a fundamental component of the brain's control of energy homeostasis. Medications targeting the 5-HT pathway have been at the forefront of obesity treatment for the past 15years. Pharmacological agents targeting 5-HT receptors (5-HTR), in combination with genetic models of 5-HTR manipulation, have uncovered a role for specific 5-HTRs in energy balance and reveal the 5-HT2CR as the principal 5-HTR mediating this homeostatic process. Capitalising on this neurophysiological machinery, 5-HT2CR agonists improve obesity and glycaemic control in patient populations. The underlying therapeutic mechanism has been probed using model systems and appears to be achieved primarily through 5-HT2CR modulation of the brain melanocortin circuit via activation of pro-opiomelanocortin neurones signalling at melanocortin4 receptors. Thus, 5-HT2CR agonists offer a means to improve obesity and type 2 diabetes, which are conditions that now represent global challenges to human health.",
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note = "Date of Acceptance: 23/04/15 Acknowledgements The present study was supported by the Wellcome Trust (093566 to LKB and LKH; 098012 to LKH). We wish to acknowledge Patricia Bain for her support in graphics design. Note A Study to Evaluate the Effect of Long-term Treatment With BELVIQ (Lorcaserin HCl) on the Incidence of Major Adverse Cardiovascular Events and Conversion to Type 2 Diabetes Mellitus in Obese and Overweight Subjects With Cardiovascular Disease or Multiple Cardiovascular Risk Factors (CAMELLIA-TIMI)",
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AB - The central 5-hydroxytryptamine (5-HT; serotonin) system represents a fundamental component of the brain's control of energy homeostasis. Medications targeting the 5-HT pathway have been at the forefront of obesity treatment for the past 15years. Pharmacological agents targeting 5-HT receptors (5-HTR), in combination with genetic models of 5-HTR manipulation, have uncovered a role for specific 5-HTRs in energy balance and reveal the 5-HT2CR as the principal 5-HTR mediating this homeostatic process. Capitalising on this neurophysiological machinery, 5-HT2CR agonists improve obesity and glycaemic control in patient populations. The underlying therapeutic mechanism has been probed using model systems and appears to be achieved primarily through 5-HT2CR modulation of the brain melanocortin circuit via activation of pro-opiomelanocortin neurones signalling at melanocortin4 receptors. Thus, 5-HT2CR agonists offer a means to improve obesity and type 2 diabetes, which are conditions that now represent global challenges to human health.

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