Phosphodiesterase 4 Inhibition Attenuates Diet-Induced Obesity and Activates BAT Thermogenic Pathways Through Central Mechanisms.
Hellen Veida-Raposo
M. A. C. de Andrade
P. Zarpellon
Michele de Souza Seixas
Luiza Mendonça Duarte
Rosa Elvira Alarcón-Yempén
A. D. de Jesus
L. C. Alberici
R. M. Leão
J. Antunes-Rodrigues
F. D. de Paula
L. Elias
Medicine
Abstract
ARTICLE HIGHLIGHTS Metabolic alterations in obesity encompass impaired thermogenesis and sympathetic activity, underscoring the need for new metabolic targets to treat this disease. This study tested whether inhibition of PDE4 by rolipram enhances energy expenditure and brown adipose tissue activity. Rolipram reduced body weight and adiposity and increased brown adipose tissue temperature, UCP1 protein levels, noradrenaline levels, and enhanced excitability of hypothalamic paroventricular nucleus neurons. These findings suggest that central PDE4 inhibition promotes brown adipose tissue thermogenic activity and contributes to the metabolic effects of rolipram.