Beige adipocyte maintenance is regulated by autophagy-induced mitochondrial clearance
Open accessAbstract
Beige adipocytes gained much attention as an alternative cellular target in anti-obesity therapy. While recent studies have identified a number of regulatory circuits that promote beige adipocyte differentiation, the molecular basis of beige adipocyte maintenance remains unknown. Here, we demonstrate that beige adipocytes progressively lose their morphological and molecular characteristics after withdrawing external stimuli and directly acquire white-like characteristics bypassing an intermediate precursor stage. The beige-to-white adipocyte transition is tightly coupled to a decrease in mitochondria, increase in autophagy, and activation of MiT/TFE transcription factor-mediated lysosome biogenesis. The autophagy pathway is crucial for mitochondrial clearance during the transition; inhibiting autophagy by uncoupled protein 1 (UCP1(+))-adipocyte-specific deletion of Atg5 or Atg12 prevents beige adipocyte loss after withdrawing external stimuli, maintaining high thermogenic capacity and protecting against diet-induced obesity and insulin resistance. The present study uncovers a fundamental mechanism by which autophagy-mediated mitochondrial clearance controls beige adipocyte maintenance, thereby providing new opportunities to counteract obesity.
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Ucp1 conditional deletion of Atg5 or Atg12 is sufficient to prevent the dedifferentiation of beige adipocytes.
“As proof of the importance of (mito)autophagy in the process, Ucp1 conditional deletion of Atg5 or Atg12 is sufficient to prevent the dedifferentiation of beige adipocytes [224].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [224]
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- Authors
- Altshuler-Keylin, S., Shinoda, K., Hasegawa, Y., Ikeda, K., Hong, H., Kang, Q., Yang, Y., Perera, R. M., Debnath, J., & Kajimura, S.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Kajimura, Shingo
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 24
- Issue
- 3
- Pages
- 402-419
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5023491
- OpenAlex
- W2517759674
- Cited by
- 349
- References
- 68
- Citations by year
- 2026: 22 · 2025: 28 · 2024: 24 · 2023: 36 · 2022: 44 · 2021: 43 · 2020: 55 · 2019: 43 · 2018: 24 · 2017: 23 · 2016: 6
- FWCI
- 25.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 377 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (DK97441, DK108822, CA126792)
- Diabetes and Endocrine-Related Disease Center (DERC) (DK63720)
- Pew Charitable Trust
- Japan Science and Technology Agency
- American Cancer Society
- Pancreatic Cancer Action Network
- AACR Career Development
- American Heart Association (AHA) (15PRE23050029)
- California Institute for Regenerative Medicine (CIRM) (TG2-01153)
- Larry L. Hillblom Foundation (LLHF) (2014-D-025-FEL)
- Manpei Suzuki Diabetes Foundation
- China Scholarship Council (CSC) (201506350063)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- beige adipocytes, autophagy, mitochondrial clearance, lysosomal biogenesis, thermogenesis, diet-induced obesity, insulin resistance, UCP1, ATG5, ATG12, obesity treatment
- MeSH terms
- Adipocytes, Beige, Autophagy-Related Proteins, Cyclic AMP, Animals, Autophagy, Organelle Biogenesis, Insulin Resistance, Lysosomes, Mitochondria, Obesity, Phenotype, Signal Transduction, Gene Deletion, Cyclic AMP-Dependent Protein Kinases, Cell Shape, Mice, Microphthalmia-Associated Transcription Factor, Adipocytes, White, Adrenergic beta-3 Receptor Agonists, Diet, High-Fat
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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