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A Combination of a Dopamine Receptor 2 Agonist and a Kappa Opioid Receptor Antagonist Synergistically Reduces Weight in Diet-Induced Obese Rodents.
Cicuéndez, Beatriz; Pérez-García, Javier; Folgueira, Cintia.
Affiliation
  • Cicuéndez B; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
  • Pérez-García J; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
  • Folgueira C; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
Nutrients ; 16(3)2024 Jan 31.
Article in En | MEDLINE | ID: mdl-38337707
ABSTRACT
As the global obesity rate increases, so does the urgency to find effective anti-obesity drugs. In the search for therapeutic targets, central nervous system (CNS) mechanisms engaged in the regulation of energy expenditure and food intake, such as the opioid and dopamine systems, are crucial. In this study, we examined the effect on body weight of two drugs bromocriptine (BC), a D2R receptor agonist, and PF-04455242, a selective κ opioid receptor (KOR) antagonist. Using diet-induced obese (DIO) rats, we aimed to ascertain whether the administration of BC and PF-04455242, independently or in combination, could enhance body weight loss. Furthermore, the present work demonstrates that the peripheral coadministration of BC and PF-04455242 enhances the reduction of weight in DIO rats and leads to a decrease in adiposity in a food-intake-independent manner. These effects were based on heightened energy expenditure, particularly through the activation of brown adipose tissue (BAT) thermogenesis. Overall, our findings indicate that the combination of BC and PF-04455242 effectively induces body weight loss through increased energy expenditure by increasing thermogenic activity and highlight the importance of the combined use of drugs to combat obesity.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sulfonamides / Biphenyl Compounds / Receptors, Opioid, kappa / Narcotic Antagonists Type of study: Etiology_studies Limits: Animals Language: En Journal: Nutrients Year: 2024 Document type: Article Affiliation country: España

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sulfonamides / Biphenyl Compounds / Receptors, Opioid, kappa / Narcotic Antagonists Type of study: Etiology_studies Limits: Animals Language: En Journal: Nutrients Year: 2024 Document type: Article Affiliation country: España