Affiliation:
1. Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain
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.
Funder
“la Caixa” Foundation
Sara Borrell
Novo Nordisk New Investigator Award in Basic Sciences 2023
EFSD/Lilly Young Investigator Award 2022
Society for Endocrinology/Early Career Grant 2022
FSEEN/Jóvenes endocrinólogos 2022
Instituto de Salud Carlos III
Ministerio de Ciencia e Innovación
MICIN/AEI
Subject
Food Science,Nutrition and Dietetics
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