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

Cell Metab. 2017 Apr 4;25(4):811-822.e4. doi: 10.1016/j.cmet.2017.03.002.


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.

MeSH terms

  • Adipocytes, Beige / drug effects
  • Adipocytes, Beige / metabolism*
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Cell Respiration / drug effects
  • Creatine / metabolism*
  • Epididymis / metabolism
  • Fatty Acids / metabolism
  • Inguinal Canal / physiology
  • Male
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Oxidative Phosphorylation / drug effects
  • Patch-Clamp Techniques*
  • Protons
  • Purine Nucleotides / pharmacology
  • Receptors, Adrenergic, beta-3 / metabolism
  • Uncoupling Protein 1 / metabolism*


  • Fatty Acids
  • Protons
  • Purine Nucleotides
  • Receptors, Adrenergic, beta-3
  • Uncoupling Protein 1
  • Creatine