通过激活AMPK信号传导和线粒体功能，PDE3B KO脂肪组织中的白色变成米色。,Scientific Reports

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通过激活AMPK信号传导和线粒体功能，PDE3B KO脂肪组织中的白色变成米色。
Scientific Reports ( IF 3.8 ) Pub Date : 2017-01-13 , DOI: 10.1038/srep40445
Youn Wook Chung , Faiyaz Ahmad , Yan Tang , Steven C. Hockman , Hyun Jung Kee , Karin Berger , Emilia Guirguis , Young Hun Choi , Dan M. Schimel , Angel M. Aponte , Sunhee Park , Eva Degerman , Vincent C. Manganiello

了解白色脂肪组织（WAT）中的米色脂肪细胞群增加的机制反映了对抗肥胖和糖尿病的潜在策略。环状单磷酸腺苷（cAMP）在米色表型的发展及其热生成程序的激活中非常重要。为了研究环核苷酸对能量稳态机制的影响，通过环核苷酸磷酸二酯酶3b（Pde3b）基因的靶向失活产生了小鼠，该基因编码PDE3B，该酶催化cAMP和cGMP的水解并在调节能量稳态的组织中高度表达。包括脂肪组织，肝脏和胰腺。在SvJ129背景下的PDE3B KO小鼠的附睾白色脂肪组织（eWAT）中，cAMP /蛋白激酶A（PKA）和AMP激活的蛋白激酶（AMPK）信号通路被激活，导致“褐变”表型，高脂饮食下体重增加较小，脂肪沉积较小，β-氧化增加脂肪酸（FAO）和耗氧量。此处报道的结果表明，PDE3B和/或其下游信号传导伙伴可能是脂肪组织中能量代谢的重要调节剂，并且是治疗肥胖症，糖尿病及其相关代谢紊乱的潜在治疗靶标。

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White to beige conversion in PDE3B KO adipose tissue through activation of AMPK signaling and mitochondrial function.

Understanding mechanisms by which a population of beige adipocytes is increased in white adipose tissue (WAT) reflects a potential strategy in the fight against obesity and diabetes. Cyclic adenosine monophosphate (cAMP) is very important in the development of the beige phenotype and activation of its thermogenic program. To study effects of cyclic nucleotides on energy homeostatic mechanisms, mice were generated by targeted inactivation of cyclic nucleotide phosphodiesterase 3b (Pde3b) gene, which encodes PDE3B, an enzyme that catalyzes hydrolysis of cAMP and cGMP and is highly expressed in tissues that regulate energy homeostasis, including adipose tissue, liver, and pancreas. In epididymal white adipose tissue (eWAT) of PDE3B KO mice on a SvJ129 background, cAMP/protein kinase A (PKA) and AMP-activated protein kinase (AMPK) signaling pathways are activated, resulting in "browning" phenotype, with a smaller increases in body weight under high-fat diet, smaller fat deposits, increased β-oxidation of fatty acids (FAO) and oxygen consumption. Results reported here suggest that PDE3B and/or its downstream signaling partners might be important regulators of energy metabolism in adipose tissue, and potential therapeutic targets for treating obesity, diabetes and their associated metabolic disorders.

更新日期：2017-01-31

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