Mitochondrial Patch Clamp of Beige Adipocytes Reveals UCP1-Positive and UCP1-Negative Cells Both Exhibiting Futile Creatine Cycling

Ambre M. Bertholet, Lawrence Kazak, Edward T. Chouchani, Marta G. Bogaczynska, Ishan Paranjpe, Gabrielle L. Wainwright, Alexandre Be´tourne´, Shingo Kajimura, Bruce M. Spiegelman, and Yuriy Kirichok
Cell Metabolism
Publication Date: 
Tue, 2017-04-04
University of California, San Francisco
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.
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