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

Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Ambre M. Bertholet, Lawrence Kazak, Edward T. Chouchani, Marta G. Bogaczyńska, Ishan Paranjpe, Gabrielle L. Wainwright, Alexandre Bétourné, Shingo Kajimura, Bruce M. Spiegelman, Yuriy Kirichok
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.

Graphical abstract

Teaser

Using patch-clamping and bioenergetics analyses of isolated mitochondria, Bertholet et al. investigated the thermogenic mechanisms of beige fat and identified two distinct types of beige adipocytes: UCP1 positive and UCP1 negative. Beige adipocytes of abdominal fat are mostly UCP1 negative but possess thermogenic capacity associated with a futile creatine cycle.


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