Obesity increases the risk of mortality because of metabolic sequelae such as type 2 diabetes and cardiovascular disease¹. Thermogenesis by adipocytes can counteract obesity and metabolic diseases^2,3. In thermogenic fat, creatine liberates a molar excess of mitochondrial ADP—purportedly via a phosphorylation cycle⁴—to drive thermogenic respiration. However, the proteins that control this futile creatine cycle are unknown. Here we show that creatine kinase B (CKB) is indispensable for thermogenesis resulting from the futile creatine cycle, during which it traffics to mitochondria using an internal mitochondrial targeting sequence. CKB is powerfully induced by thermogenic stimuli in both mouse and human adipocytes. Adipocyte-selective inactivation of Ckb in mice diminishes thermogenic capacity, increases predisposition to obesity, and disrupts glucose homeostasis. CKB is therefore a key effector of the futile creatine cycle.

由于代谢后遗症，如 2 型糖尿病和心血管疾病¹ ，肥胖会增加死亡风险。脂肪细胞产热可以抵消肥胖和代谢疾病^2,3。在产热脂肪中，肌酸释放出摩尔过量的线粒体 ADP（据称是通过磷酸化循环⁴ ）来驱动产热呼吸。然而，控制这种无效肌酸循环的蛋白质是未知的。在这里，我们表明肌酸激酶 B (CKB) 对于无效的肌酸循环产生的产热是必不可少的，在此期间它使用内部线粒体靶向序列运输到线粒体。CKB 受到小鼠和人类脂肪细胞中产热刺激的强烈诱导。脂肪细胞选择性失活小鼠体内的Ckb降低了产热能力，增加了肥胖的倾向，并破坏了葡萄糖稳态。因此，CKB 是无效肌酸循环的关键效应器。