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Article

A Combination of a Dopamine Receptor 2 Agonist and a Kappa Opioid Receptor Antagonist Synergistically Reduces Weight in Diet-Induced Obese Rodents

by
Beatriz Cicuéndez
,
Javier Pérez-García
and
Cintia Folgueira
*
Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
Nutrients 2024, 16(3), 424; https://doi.org/10.3390/nu16030424
Submission received: 8 January 2024 / Revised: 25 January 2024 / Accepted: 29 January 2024 / Published: 31 January 2024
(This article belongs to the Special Issue Featured Articles on Nutrition and Obesity Management (2nd Edition))

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.
Keywords: obesity; pharmacological treatment; weight loss; synergistic treatment obesity; pharmacological treatment; weight loss; synergistic treatment

Share and Cite

MDPI and ACS Style

Cicuéndez, B.; Pérez-García, J.; Folgueira, C. A Combination of a Dopamine Receptor 2 Agonist and a Kappa Opioid Receptor Antagonist Synergistically Reduces Weight in Diet-Induced Obese Rodents. Nutrients 2024, 16, 424. https://doi.org/10.3390/nu16030424

AMA Style

Cicuéndez B, Pérez-García J, Folgueira C. A Combination of a Dopamine Receptor 2 Agonist and a Kappa Opioid Receptor Antagonist Synergistically Reduces Weight in Diet-Induced Obese Rodents. Nutrients. 2024; 16(3):424. https://doi.org/10.3390/nu16030424

Chicago/Turabian Style

Cicuéndez, Beatriz, Javier Pérez-García, and Cintia Folgueira. 2024. "A Combination of a Dopamine Receptor 2 Agonist and a Kappa Opioid Receptor Antagonist Synergistically Reduces Weight in Diet-Induced Obese Rodents" Nutrients 16, no. 3: 424. https://doi.org/10.3390/nu16030424

APA Style

Cicuéndez, B., Pérez-García, J., & Folgueira, C. (2024). A Combination of a Dopamine Receptor 2 Agonist and a Kappa Opioid Receptor Antagonist Synergistically Reduces Weight in Diet-Induced Obese Rodents. Nutrients, 16(3), 424. https://doi.org/10.3390/nu16030424

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