Theobromine alleviates diet-induced obesity in mice via phosphodiesterase-4 inhibition

被引:28
作者
Jang, Myeong Hwan [1 ]
Mukherjee, Sulagna [1 ]
Choi, Min Ji [1 ]
Kang, Nam Hyeon [1 ]
Pham, Huong Giang [1 ]
Yun, Jong Won [1 ]
机构
[1] Daegu Univ, Dept Biotechnol, Gyongsan 38453, Gyeongbuk, South Korea
基金
新加坡国家研究基金会;
关键词
Adipose tissue; Anti-obesity; Theobromine; Phosphodiesterase; Fat browning; ADIPOSE-TISSUE; CYCLIC-AMP; BROWN; ADIPOCYTE; METHYLXANTHINE; ADIPOGENESIS; ANTAGONISM; ADENOSINE; LIPOLYSIS; CAFFEINE;
D O I
10.1007/s00394-020-02184-6
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
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.
引用
收藏
页码:3503 / 3516
页数:14
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