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Small-Molecule Neuromedin U Receptor 2 Agonists Suppress Food Intake and Decrease Visceral Fat in Animal Models.

Catherine M Sampson1, James M Kasper1, Daniel E Felsing1

  • 1Center for Addiction Research Department of Pharmacology and Toxicology University of Texas Medical Branch Galveston TX USA.

Pharmacology Research & Perspectives
|August 29, 2018
PubMed
Summary

New small-molecule agonists targeting neuromedin U receptor 2 (NMUR2) effectively reduced food intake and body weight in obese mice. These findings highlight NMUR2 as a promising target for developing novel obesity therapeutics.

Keywords:
Neuromedin U receptor 2calciumcyclic AMPfeedinghigh‐fat dietobesitysmall‐molecule agonist

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Area of Science:

  • Pharmacology
  • Endocrinology
  • Metabolic Disorders

Background:

  • Obesity is a significant public health issue requiring more effective treatments.
  • Neuromedin U (NMU) suppresses appetite and weight gain in animal models.
  • Neuromedin U receptor 2 (NMUR2) is implicated in NMU's effects on feeding behavior.

Purpose of the Study:

  • To discover and evaluate small-molecule agonists of NMUR2 for therapeutic potential in metabolic disorders.
  • To assess the in vitro signaling and in vivo efficacy of novel NMUR2 agonists.

Main Methods:

  • Synthesis of two small-molecule NMUR2 agonists (NY0116 and NY0128).
  • In vitro assessment of NMUR2 signaling (cAMP and calcium).
  • In vivo testing in obese mice to evaluate effects on diet consumption, body weight, and visceral adipose tissue (VAT).

Main Results:

  • Both compounds demonstrated NMUR2 agonism, decreasing cAMP and stimulating calcium signaling in vitro.
  • Acute administration reduced high-fat diet consumption.
  • Repeated administration led to decreased body weight and reduced visceral adipose tissue percentage in obese mice.

Conclusions:

  • Small-molecule NMUR2 agonists show efficacy in preclinical models for reducing food intake, body weight, and fat content.
  • NMUR2 represents a promising therapeutic target for managing metabolic disorders like obesity.