Mitochondrial Patch Clamp of Beige Adipocytes Reveals UCP1-Positive and UCP1-Negative Cells Both Exhibiting Futile Creatine Cycling
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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 (I H). All inguinal beige adipocytes had robust UCP1-dependent I H comparable to brown fat, but it was about three times less sensitive to purine nucleotide inhibition. Strikingly, only ∼15% of epididymal beige adipocytes had I H, while in the rest UCP1-dependent I H 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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Adipose tissue depots possess alternative futile cycles for increasing energy expenditure independent of UCP1.
“Studies within the past few years have demonstrated that adipose tissue depots possess alternative futile cycles for increasing energy expenditure independent of UCP1 (10, 58).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [10]
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References 51 · Cited by 225
- Authors
- Bertholet, A. M., Kazak, L., Chouchani, E. T., Bogaczyńska, M. G., Paranjpe, I., Wainwright, G. L., Bétourné, A., Kajimura, S., Spiegelman, B. M., & Kirichok, Y.
- Affiliations
- University of California, San Francisco (US)
- Harvard University (US)
- Corresponding author
- Kirichok, Yuriy
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 25
- Issue
- 4
- Pages
- 811-822.e4
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5448977
- OpenAlex
- W2604817598
- Cited by
- 225
- References
- 51
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 16 · 2023: 14 · 2022: 23 · 2021: 32 · 2020: 38 · 2019: 30 · 2018: 26 · 2017: 19 · 2012: 1
- FWCI
- 22.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (5R01GM107710, DK 31405)
- JPB Foundation
- Canadian Institutes of Health Research
- Human Frontier Science Program
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- beige adipocytes, UCP1, mitochondrial uncoupling, proton leak, thermogenesis, brown adipose tissue, white adipose tissue browning, mitochondrial membrane potential, cold acclimation, inguinal adipose tissue, epididymal adipose tissue
- MeSH terms
- Adipocytes, Beige, Uncoupling Protein 1, Animals, Adipose Tissue, Brown, Creatine, Epididymis, Fatty Acids, Inguinal Canal, Male, Mitochondria, Oxidative Phosphorylation, Protons, Purine Nucleotides, Patch-Clamp Techniques, Cell Respiration, Receptors, Adrenergic, beta-3, Mice
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