Mitochondrial Patch Clamp of Beige Adipocytes Reveals UCP1-Positive and UCP1-Negative Cells Both Exhibiting Futile Creatine Cycling.
Mitochondrial Patch Clamp of Beige Adipocytes Reveals UCP1-Positive and UCP1-Negative Cells Both Exhibiting Futile Creatine Cycling.
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DOI：
10.1016/j.cmet.2017.03.002
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发表时间：
2017-04-04
期刊：
影响因子：
29
通讯作者：
Kirichok Y
中科院分区：
文献类型：
--
作者：
Bertholet AM;Kazak L;Chouchani ET;Bogaczyńska MG;Paranjpe I;Wainwright GL;Bétourné A;Kajimura S;Spiegelman BM;Kirichok Y
寒冷和其他环境因素诱导白色脂肪库的“布朗宁”--形成与棕色脂肪在形态和功能上相似的米色脂肪细胞。与棕色脂肪类似，假定米色脂肪细胞表达线粒体解偶联蛋白1（UCP 1），并且由于UCP 1介导的H+穿过线粒体内膜泄漏而产热。然而，这一假设从未被直接验证过。在这里，我们膜片钳米色和棕色脂肪的线粒体内膜，以提供它们的产热H+泄漏（IH）的直接比较。所有腹股沟米色脂肪细胞都具有与棕色脂肪相当的强大的UCP 1依赖性IH，但它对嘌呤核苷酸抑制的敏感性低约三倍。引人注目的是，只有15%的附睾米色脂肪细胞有IH，而在其余的UCP 1依赖性IH是检测不到的。尽管UCP 1在大多数的附睾米色脂肪细胞的情况下，这些细胞采用显着的肌酸循环作为UCP 1独立的产热机制。
Cold and other environmental factors induce “browning” of white fat depots — development of beige adipocytes with morphological and functional resemblance to brown fat. Similar to brown fat, beige adipocytes are assumed to express mitochondrial uncoupling protein 1 (UCP1) and are thermogenic due to the UCP1-mediated H+ leak across the inner mitochondrial membrane. However, this assumption has never been tested directly. Herein we patch-clamped the inner mitochondrial membrane of beige and brown fat to provide a direct comparison of their thermogenic H+ leak (IH). All inguinal beige adipocytes had robust UCP1-dependent IH comparable to brown fat, but it was about three times less sensitive to purine nucleotide inhibition. Strikingly, only ~15% of epididymal beige adipocytes had IH, while in the rest UCP1-dependent IH was undetectable. Despite the absence of UCP1 in the majority of epididymal beige adipocytes, these cells employ prominent creatine cycling as a UCP1-independent thermogenic mechanism.