Cardiovascular and Pulmonary Branch (CPB), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland, 20892, USA.
Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases (SIRIC), Yonsei University College of Medicine, Seoul, 03722, Korea.
Sci Rep. 2017 Jan 13;7:40445. doi: 10.1038/srep40445.
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.
了解在白色脂肪组织（WAT）中增加米色脂肪细胞群体的机制反映了对抗肥胖和糖尿病的潜在策略。环腺苷酸（cAMP）在米色表型的发展和其产热程序的激活中非常重要。为了研究环核苷酸对能量动态平衡机制的影响，通过靶向失活编码 PDE3B 的环核苷酸磷酸二酯酶 3b（Pde3b）基因生成了小鼠，PDE3B 是一种酶，可催化 cAMP 和 cGMP 的水解，在调节能量动态平衡的组织中高度表达，包括脂肪组织、肝脏和胰腺。在 SvJ129 背景下 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“褐色化”表型，高脂肪饮食下体重增加较小，脂肪沉积较小，脂肪酸（FAO）β-氧化和耗氧量增加。这里报道的结果表明，PDE3B 和/或其下游信号伙伴可能是脂肪组织能量代谢的重要调节剂，是治疗肥胖、糖尿病及其相关代谢紊乱的潜在治疗靶点。
