Cellular Origins of Beige Fat Cells Revisited
- 16 September 2019
- journal article
- research article
- Published by American Diabetes Association in Diabetes
- Vol. 68 (10), 1874-1885
- https://doi.org/10.2337/db19-0308
Abstract
Activated beige adipocytes have therapeutic potential due to their ability to improve glucose and lipid homeostasis. To date, the origin of beige adipocytes remains enigmatic. Whether beige cells arise through de novo differentiation from resident precursors or through reprogramming of mature white adipocytes has been a topic of intense discussion. Here, we offer our perspective on the natural origin of beige adipocytes in mice. In particular, we revisit recent lineage-tracing studies that shed light on this issue and offer new insight into how environmental housing temperatures early in life influence the mode of beige adipocyte biogenesis upon cold exposure later in life. We suggest a unified model in which beige adipocytes (UCP1+ multilocular cells) in rodents initially arise predominantly from progenitors (i.e., de novo beige adipogenesis) upon the first exposure to cold temperatures and then interconvert between “dormant beige” and “active beige” phenotypes (i.e., beige cell activation) upon subsequent changes in environmental temperature. Importantly, we highlight experimental considerations needed to visualize de novo adipogenesis versus beige cell activation in mice. A precise understanding of the cellular origins of beige adipocytes emanating in response to physiological and pharmacological stimuli may better inform therapeutic strategies to recruit beige adipocytes in vivo.Keywords
Funding Information
- American Heart Association (16POST26420136, 19CDA34670007)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01-DK107788, R03-HD095414, DK-104789, R01-DK55758, R01-DK099110, P01-DK088761, 16GRNT30790006)
This publication has 59 references indexed in Scilit:
- Bi-directional interconversion of brite and white adipocytesNature, 2013
- Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fatNature Medicine, 2013
- Human BAT Possesses Molecular Signatures That Resemble Beige/Brite CellsPLOS ONE, 2012
- Dedifferentiation, transdifferentiation and reprogramming: three routes to regenerationNature Reviews Molecular Cell Biology, 2011
- Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in miceJCI Insight, 2011
- The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiationAmerican Journal of Physiology-Endocrinology and Metabolism, 2010
- Chronic Peroxisome Proliferator-activated Receptor γ (PPARγ) Activation of Epididymally Derived White Adipocyte Cultures Reveals a Population of Thermogenically Competent, UCP1-containing Adipocytes Molecularly Distinct from Classic Brown AdipocytesOnline Journal of Public Health Informatics, 2010
- PRDM16 controls a brown fat/skeletal muscle switchNature, 2008
- Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineagesProceedings of the National Academy of Sciences of the United States of America, 2007
- Strain-Specific Response to 3-Adrenergic Receptor Agonist Treatment of Diet-Induced Obesity in MiceEndocrinology, 1997