Can neuropeptides treat obesity? A review of neuropeptides and their potential role in the treatment of obesity

Abstract

Obesity is a major worldwide public health issue. The physiological systems that regulate body weight are thus of great interest as targets for anti-obesity agents. Peptidergic systems are critical to the regulation of energy homeostasis by key regions in the hypothalamus and brainstem. A number of neuropeptide systems have therefore been investigated as potential treatments for obesity. Blocking orexigenic peptide signals such as neuropeptide Y, melanin-concentrating hormone, orexins, relaxin-3 and galanin-like peptide or stimulating anorectic signalling pathways used by peptides such as the melanocortins, ciliary neurotrophic factor and brain-derived neurotrophic factor, are approaches that have shown some promise, but which have also highlighted possible concerns. Manipulation of central peptidergic systems poses a number of therapeutic problems, including brain access and side effects. Given that the homeostatic defence of body weight may limit the effectiveness of any single-target therapy developed, a combination therapy approach may offer the best hope for the effective prevention and treatment of obesity.

Linked articles: This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7.

Keywords: anorectic; hypothalamus; neuropeptides; obesity; orexigenic.

Figure 1

Schematic diagram illustrating the neuropeptidergic signalling pathways regulating energy homeostasis. Hypothalamic nuclei integrate and process signals of energy homeostasis from the periphery and other CNS regions and induce appropriate changes in appetite and energy expenditure. Peptides coloured blue are orexigenic, promoting food intake, while peptides coloured red are anorexigenic, promoting satiety. Receptors are in white boxes. Purple indicates neurons, which can be either orexigenic or anorexigenic. Non-peptidergic neurotransmitters are not included in this diagram for clarity. The peripheral factors in the diagram are reviewed elsewhere (Murphy et al., 2006). CNTF-R, ciliary neurotrophic factor receptor; GalR1/2/3, galanin receptors 1,2 and 3; GHS-R, growth hormone secretagogue receptor; INS-R, insulin receptor; MC3/4-R, melanocortin 3/4 receptors; NAc, nucleus accumbens; OB-R, leptin receptor; RXFP3, relaxin/insulin-like family peptide receptor 3; TRkB-R, tyrosine-related kinase B receptor; VTA, ventral tegmental area; Y1/Y5-R, neuropeptide Y₁/Y₅ receptors.