title: Mitochondrial Patch Clamp of Beige Adipocytes Reveals UCP1-Positive and UCP1-Negative Cells Both Exhibiting Futile Creatine Cycling.
abstract: 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 IHcomparable 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 IHwas 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.
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Ambre M
authors.initials: AM
authors.lastname: Bertholet
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kazak
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Chouchani
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Marta G
authors.initials: MG
authors.lastname: Bogaczyńska
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Ishan
authors.initials: I
authors.lastname: Paranjpe
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Gabrielle L
authors.initials: GL
authors.lastname: Wainwright
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bétourné
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kajimura
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Spiegelman
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: yuriy.kirichok@ucsf.edu.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Kirichok
mesh_terms: D000069797:Adipocytes, Beige / Q000187:drug effects / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D003401:Creatine / Q000378:metabolism*; D004822:Epididymis / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D007264:Inguinal Canal / Q000502:physiology; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011522:Protons; D011685:Purine Nucleotides / Q000494:pharmacology; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D011522:Protons; D011685:Purine Nucleotides; D022702:Receptors, Adrenergic, beta-3; D000071256:Uncoupling Protein 1; D003401:Creatine