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Serotonergic Control of Metabolic Homeostasis


Serotonergic Control of Metabolic Homeostasis

Steven C Wyler et al. Front Cell Neurosci.


New treatments are urgently needed to address the current epidemic of obesity and diabetes. Recent studies have highlighted multiple pathways whereby serotonin (5-HT) modulates energy homeostasis, leading to a renewed interest in the identification of 5-HT-based therapies for metabolic disease. This review aims to synthesize pharmacological and genetic studies that have found diverse functions of both central and peripheral 5-HT in the control of food intake, thermogenesis, and glucose and lipid metabolism. We also discuss the potential benefits of targeting the 5-HT system to combat metabolic disease.

Keywords: adipose tissue; diabetes; feeding; gluconeogenesis; obesity; pancreas; serotonin.


Figure 1
Figure 1
Brain 5-HT acts on central melanocortin neurons to suppress food intake. Melanocortin receptor (MC3/4R) neurons integrate signals from two reciprocal populations of neurons within the arcuate nucleus to promote satiety. Activation of 5-HT2c increases the activity of anorexigenic proopiomelanocortin (POMC) neurons, whereas activation of 5-HT1B inhibits the orexigenic NPY/AgRP neurons.
Figure 2
Figure 2
Central and peripheral 5-HT acts on multiple organs to regulate metabolic homeostasis. 5-HT in the central nervous system acts on multiple nodes of the neuroaxis (hypothalamus, brain stem and the spinal cord) to regulate satiety, hepatic glucose uptake and adaptation to cold exposure. Dashed line from brain to liver indicates the mechanism regulating hepatic glucose uptake is unknown. Peripheral 5-HT produced by intestinal enterochromaffin cells, pancreatic islets and adipose tissue exerts local and/or systemic control of lipid and glucose homeostasis though distinct 5-HT receptors. Abbreviations: ARC, Arcuate nucleus; PVN, Paraventricular nucleus; RN, Raphe nuclei; IML, Intermediolateral nucleus.

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