Small‐Molecule Neuromedin U Receptor 2 Agonists Suppress Food Intake and Decrease Visceral Fat in Animal Models
Autor: | Na Ye, Erik Rytting, Igor Patrikeev, Daniel E. Felsing, Pingyuan Wang, James M. Kasper, Jia Zhou, Jonathan D. Hommel, Sweta Raval, Catherine M. Sampson, John A. Allen |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Adult Male obesity Side effect Neuropeptide Adipose tissue Pharmacology Intra-Abdominal Fat Diet High-Fat high‐fat diet Rats Sprague-Dawley 03 medical and health sciences Neuromedin U receptor Eating 0302 clinical medicine In vivo Neuromedin U receptor 2 Medicine Animals Humans cyclic AMP General Pharmacology Toxicology and Pharmaceutics 2. Zero hunger calcium business.industry Body Weight Neuropeptides Original Articles medicine.disease Obesity small‐molecule agonist 3. Good health Rats Receptors Neurotransmitter Mice Inbred C57BL Disease Models Animal 030104 developmental biology HEK293 Cells Treatment Outcome Neurology Original Article Anti-Obesity Agents medicine.symptom business Weight gain 030217 neurology & neurosurgery Neuromedin U feeding |
Zdroj: | Pharmacology Research & Perspectives |
ISSN: | 2052-1707 |
Popis: | Obesity is a growing public health concern, with 37.5% of the adult population in need of therapeutics that are more efficacious with a better side effect profile. An innovative target in this regard is neuromedin U, a neuropeptide shown to suppress food intake and attenuate weight gain in animal models. These effects of neuromedin U on feeding behavior are thought to be related to agonism at the centrally expressed neuromedin U receptor 2 (NMUR2). As peptides present unique challenges that limit their therapeutic potential, the discovery of small‐molecule NMUR2 agonists is needed to validate the targets therapeutic value, but to date, none have been evaluated in any animal model of disease. We therefore assessed two small‐molecule NMUR2 agonists for their in vitro signaling and their in vivo efficacy. The NMUR2 agonists were synthesized and both NMUR2 agonists, NY0116 and NY0128, decreased cAMP while stimulating calcium signaling in stably expressing NMUR2 HEK293 cells. When small‐molecule NMUR2 agonists were tested in vivo, acute administration significantly decreased high‐fat diet consumption. Repeated administration of the compounds decreased body weight and more specifically, decreased the percentage of visceral adipose tissue (VAT) in obese mice. These results have confirmed small‐molecule NMUR2 agonists are efficacious in animal models to decrease fat content, food intake, and body weight, suggesting NMUR2 is a promising therapeutic target for metabolic disorders. |
Databáze: | OpenAIRE |
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