Cell Metabolism
Volume 25, Issue 4, 4 April 2017, Pages 811-822.e4
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Article
Mitochondrial Patch Clamp of Beige Adipocytes Reveals UCP1-Positive and UCP1-Negative Cells Both Exhibiting Futile Creatine Cycling

https://doi.org/10.1016/j.cmet.2017.03.002Get rights and content
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Highlights

  • Patch clamp is used to directly measure mitochondrial H+ leak in beige adipocytes

  • Two types of beige adipocytes are identified: UCP1 positive and UCP1 negative

  • Both types of beige adipocytes display a robust futile creatine cycle

  • Abdominal beige fat, while mostly UCP1 negative, has clear thermogenic capacity

Summary

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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