The DOI matches its Crossref record; 66 of the 68 references it cites were found in a registry or an index.
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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“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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Adipose-tissue plasticity in health and disease
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Metadata
- 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 (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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
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