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PRDM16 controls a brown fat/skeletal muscle switch
Patrick Seale1, Bryan Bjork, Wenli Yang
1Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA.
Nature
|August 23, 2008
Summary
Brown fat cells originate from precursors expressing Myf5, a muscle gene. The regulator PRDM16 controls cell fate, switching between brown fat and muscle development, crucial for energy expenditure and obesity protection.
Area of Science:
- Cell Biology
- Metabolism
- Developmental Biology
Background:
- Brown adipose tissue (BAT) increases energy expenditure and combats obesity via uncoupled respiration.
- The developmental origins of brown fat cells and their relationship to other cell types remain incompletely understood.
Purpose of the Study:
- To identify the cellular precursors of brown fat cells.
- To elucidate the role of the transcriptional regulator PRDM16 in brown fat development and cell fate determination.
Main Methods:
- In vivo fate mapping to trace brown fat cell origins.
- Genetic manipulation (loss and ectopic expression) of PRDM16 in precursor cells.
- Analysis of gene expression and cellular morphology.
Main Results:
- Brown fat cells, unlike white fat cells, originate from precursors expressing the myogenic gene Myf5.
- PRDM16 acts as a crucial switch, directing cell fate between brown adipogenesis and skeletal myogenesis.
- Loss of PRDM16 in brown fat precursors leads to muscle differentiation, while its ectopic expression in myoblasts induces brown fat cell differentiation.
- PRDM16 interacts with PPAR-gamma to promote brown adipogenesis.
- Prdm16-deficient brown fat exhibits altered morphology, reduced thermogenic gene expression, and increased muscle-specific gene expression.
Conclusions:
- PRDM16 specifies the brown fat lineage from progenitors expressing myoblast markers.
- PRDM16 plays a critical role in regulating the balance between brown fat development and muscle differentiation.
- These findings provide new insights into the developmental origins of brown adipose tissue and its role in energy metabolism.
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