Journal
EUROPEAN JOURNAL OF NUTRITION
Volume 59, Issue 8, Pages 3503-3516Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00394-020-02184-6
Keywords
Adipose tissue; Anti-obesity; Theobromine; Phosphodiesterase; Fat browning
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Funding
- National Research Foundation of Korea [2019R1A2C2002163] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2019R1A2C2002163] Funding Source: Medline
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Purpose Modern science has given much attention to the treatment of obesity by activating brown adipose tissue (BAT) and browning of white adipose tissue (WAT). Recent studies have identified theobromine, a derivative of cocoa, as a potent natural component actively browning white fat cells. Here, we aimed to deduce the anti-obesity effect of theobromine involving phosphodiesterase (PDE) dependent-regulatory pathway in obese animal models. Methods For examining activity of theobromine, C57BL/6 mice were fed with high fat diet and treated with theobromine to determine the expression levels of protein markers by immunoblot analysis and gene targets by quantitative real-time PCR. Other methods used include histopathological studies, immunofluorescence and molecular docking approaches. Results Theobromine alleviated diet-induced obesity in mice by browning of iWAT and activating BAT. Further, theobromine actively interacted with PDE4D and inhibited its activity in adipose tissues and cells potentiating energy expenditure. Moreover, the regulatory action of theobromine via inhibition of PDE4D was mediated by beta 3-AR signaling pathway. Conclusion Altogether, the current results signifies critical role of theobromine in reducing obesity by regulation of lipid metabolism through inhibition of PDE4, indicating its potential as a major therapeutic medicinal compound.
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