Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity

Abstract

Obesity is one of the major social and health problems globally and often associated with various other pathological conditions. In addition to unregulated eating behaviour, circulating peptide-mediated hormonal secretion and signaling pathways play a critical role in food intake induced obesity. Amongst the many peptides involved in the regulation of food-seeking behaviour, somatostatin (SST) is the one which plays a determinant role in the complex process of appetite. SST is involved in the regulation of release and secretion of other peptides, neuronal integrity, and hormonal regulation. Based on past and recent studies, SST might serve as a bridge between central and peripheral tissues with a significant impact on obesity-associated with food intake behaviour and energy expenditure. Here, we present a comprehensive review describing the role of SST in the modulation of multiple central and peripheral signaling molecules. In addition, we highlight recent progress and contribution of SST and its receptors in food-seeking behaviour, obesity (orexigenic), and satiety (anorexigenic) associated pathways and mechanism.

Keywords: appetite; obesity; satiety; somatostatin; somatostatin receptors.

Figure 1

Overview of orexigenic and anorexigenic stimuli in association with peripheral hormones in regulation of appetite and satiety. ARC is composed of orexigenic neurons producing NPY and AgRP and anorexigenic neurons, which synthesize POMC and CART. The peripheral hormones regulate appetite via endogenous gut hormones such as CCK, GLP-1, oxyntomodulin, PYY, and PP, producing an anorexigenic effect. Ghrelin and SST have an orexigenic effect in humans and prompt food intake. In addition, SST produces dual effect (orexigenic and anorexigenic). Pointed arrows indicate activation; Blocked arrows indicate inhibition. ARC, arcuate nucleus; AgRP, agouti related peptide; CART, cocaine and amphetamine-regulated transcript; CCK, cholecystokinin; GLP-1, glucagon like peptide-1; GRP, gastrin-releasing peptide; NPY, neuropeptide Y; POMC, propiomelanocortin; PYY, peptide YY; NPY, neuropeptide Y; PP, pancreatic polypeptide; αMSH, α-melanocyte stimulating hormone; MCR, melanin-concentrating hormone receptor; SST, somatostatin.

Figure 2

Schematic presentation showing somatostatin receptors associated with different roles of somatostatin in peripheral tissues. CCK, cholecystokinin; CRH, corticotropin releasing hormone; DA, dopamine; GH, growth hormone; GIP, gastric inhibitory polypeptide; NE, norepinephrine; PP, pancreatic polypeptide; TRH, thyrotropin releasing hormone; TSH, thyroid-stimulating hormone; VEGF, vascular endothelial growth factor; VIP, vasoactive intestinal peptide.

Figure 3

Comparative assessment of somatostatin analogues in the treatment of obesity in adults and children with different route of administration. * Subcutaneous; ^# long-acting release (intramuscular); ^## long-acting drug with low-calorie diet.

Figure 4

Schematic illustration of hypothalamic regions and peripheral hormones in regulation appetite and satiety. NPY/AgRP and POMC/CART neurons in the ARC project to second-order neurons in other hypothalamic nuclei, including the PVN, DMN, VMN, and LHA. These second-order hypothalamic neurons express anorexigenic neuropeptides (CRH, TRH, OT, and BDNF) and orexigenic neuropeptides (OX and MCH), which regulate appetite and modulate energy homeostasis. In addition, the regulation of energy balance involves an integration of signaling from the hypothalamus, brain stem, and reward pathways of the mesolimbic system. SST acts via hypothalamic nuclei and pancreas. Leptin acts directly on the NTS as well as hypothalamic nuclei, and it can modulate appetite through different pathways. Green arrows indicate activations within hypothalamus; Black arrows indicate activations other than hypothalamus. ARC, arcuate nucleus; AgRP, agouti related peptide; BDNF, brain-derived neurotrophic factor; CART, cocaine- and amphetamine-regulated transcript; CB1, cannabinoid receptor 1; CCK, cholecystokinin; CRH, corticotropin, releasing hormone; DMN, dorsomedial nucleus; GhR, ghrelin receptor; GLP-1, glucagon like peptide-1; GR, glucocorticoid receptor; POMC, propiomelanocortin; PYY, peptide YY; IRN, insulin receptor neuron; LHA, lateral hypothalamic area; LepR, leptin receptor; MCH, melanin-concentrating hormone; MCR, melanin-concentrating hormone receptor; NTS, nucleus of the tractus solitaries; NPY, neuropeptide Y; OT, oxytocin; PeVN, periventicular nucleus; PVN, paraventicular nucleus; SST, somatostatin; TRH, thyrotropin-releasing hormone; VMN, ventromedial nucleus. Created with paid subscription of BioRender.com.