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The neurotransmitter serotonin (5-hydroxytryptamine) is a well-established modulator of energy balance. Both pharmacological and genetic evidence implicate the serotonin 2C receptor (5-HT(2C)R) as a critical receptor mediator of serotonin's effects on ingestive behavior. Here we characterized the effect of the novel and selective 5-HT(2C)R agonist BVT.X on(More)
Serotonin (5-HT) and leptin play important roles in the modulation of energy balance. Here we investigated mechanisms by which leptin might interact with CNS 5-HT pathways to influence appetite. Although some leptin receptor (LepRb) neurons lie close to 5-HT neurons in the dorsal raphe (DR), 5-HT neurons do not express LepRb. Indeed, while leptin(More)
The burden of type 2 diabetes and its associated premature morbidity and mortality is rapidly growing, and the need for novel efficacious treatments is pressing. We report here that serotonin 2C receptor (5-HT(2C)R) agonists, typically investigated for their anorectic properties, significantly improve glucose tolerance and reduce plasma insulin in murine(More)
An inverse relationship between brain serotonin and food intake and body weight has been known for more than 30 years. Specifically, augmentation of brain serotonin inhibits food intake, while depletion of brain serotonin promotes hyperphagia and weight gain. Through the decades, serotonin receptors have been identified and their function in the(More)
The neurotransmitter serotonin is an important regulator of energy balance. In the brain, serotonergic fibres from midbrain raphe nuclei project to key feeding centres, where serotonin acts on specific receptors to modulate the activity of various downstream neuropeptide systems and autonomic pathways and thus affects ingestive behaviour and energy(More)
The rise in the global prevalence of human obesity has emphasized the need for a greater understanding of the physiological mechanisms that underlie energy homeostasis. Numerous circulating nutritional cues and central neuromodulatory signals are integrated within the brain to regulate both short- and long-term nutritional state. The central melanocortin(More)
Maintaining glucose levels within the appropriate physiological range is necessary for survival. The identification of specific neuronal populations, within discreet brain regions, sensitive to changes in glucose concentration has led to the hypothesis of a central glucose-sensing system capable of directly modulating feeding behaviour. Glucokinase (GK) has(More)
Peptides derived from the proopiomelanocortin (POMC) precursor are critical for the normal regulation of many physiological parameters, and POMC deficiency results in severe obesity and metabolic dysfunction. Conversely, augmentation of central nervous system melanocortin function is a promising therapeutic avenue for obesity and diabetes but is confounded(More)
Pharmacological compounds enhancing serotonergic tone significantly decrease food intake and are among the most clinically efficacious treatments for obesity. However, the central mechanisms through which serotonergic compounds modulate feeding behavior have not been fully defined. The primary relay center receiving visceral gastrointestinal information in(More)
Agonists of the nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor stimulate food intake. Concordantly, neuroanatomical localization of NOP receptor mRNA has revealed it to be highly expressed in brain regions associated with the regulation of energy balance. However, the specific mechanisms and neurochemical pathways through which physiological N/OFQ(More)