Highlights
- •PROM1 expression is enriched in beige adipogenic precursor (AP) cells in subcutaneous adipose tissues.
- •Depletion of Prom1 in AP cells led to the reduced potential for beige adipogenesis.
- •PROM1-ERM axis in AP cells is critical in instigating beige adipogenesis in vitro.
- •Compared with the wild type control, Prom1 AP cell-specific knockout mice displayed impaired adaptive thermogenesis.
- •PROM1+ AP cells are instrumental in ensuing adaptive thermogenesis by maintaining the potential of beige adipogenesis.
Abstract
Background
Exposure to cold temperature stimulates the sympathetic nervous system that activates
β-adrenergic receptor signals in brown and beige adipocytes, leading to the induction
of adaptive thermogenesis in mammals. Prominin-1 (PROM1) is a pentaspan transmembrane
protein that is widely identified as a marker for stem cells, although the role of
this protein as a regulator of many intracellular signaling cascades has been recently
delineated. The main focus of the current study is to identify the previously unknown
role of PROM1 in beige adipogenesis and adaptive thermogenesis.
Methods
Prom1 whole body knockout (Prom1 KO) mice, Prom1 adipogenic progenitor (AP) cell-specific knockout (Prom1 APKO) mice and Prom1 adipocyte-specific knockout (Prom1 AKO) mice were constructed and were subject for the induction of adaptive thermogenesis.
The effect of systemic Prom1 depletion was evaluated by hematoxylin and eosin staining, immunostaining, and biochemical
analysis in vivo. Flow cytometric analysis was performed to determine the identity
of PROM1-expressing cell types, and the resultant cells were subject to beige adipogenesis
in vitro. The potential role of PROM1 and ERM in cAMP signaling was also assessed in undifferentiated
AP cells in vitro. Finally, the specific effect of Prom1 depletion on AP cell or mature adipocytes on adaptive thermogenesis was evaluated
by hematoxylin and eosin staining, immunostaining, and biochemical analysis in vivo.
Results
Prom1 KO mice displayed an impairment in cold- or β3-adrenergic agonist–induced adaptive
thermogenesis in subcutaneous adipose tissues (SAT) but not in brown adipose tissues
(BAT). By fluorescence-activated cell sorting (FACS) analysis, we identified that
PROM1 positive cells are enriched in PDGFRα+Sca1+ AP cells from SAT. Interestingly, Prom1 knockout stromal vascular fractions showed reduced PDGFRα expression, suggesting
a role of PROM1 in beige adipogenic potential. Indeed, we found that Prom1-deficient AP cells from SAT showed reduced potential for beige adipogenesis. Furthermore,
AP cell-specific depletion of Prom1, but not adipocyte-specific depletion of Prom1, displayed defects in adaptive thermogenesis as evidenced by resistance to cold-induced
browning of SAT and dampened energy expenditure in mice.
Conclusion
We found that PROM1 positive AP cells are essential for the adaptive thermogenesis
by ensuing stress-induced beige adipogenesis. Identification of PROM1 ligand might
be useful in the activation of thermogenesis that could be potentially beneficial
in combating obesity.
Graphical abstract
Graphical AbstractPROM1-ERM axis in adipogenic progenitor cells is critical in ensuing beige adipogenesis
in response to cold stimulus during adaptive thermogenesis.
Abbreviations:
PROM1 (Prominin-1), SAT (subcutaneous adipose tissues), BAT (brown adipose tissues), AP (adipogenic progenitor), UCP1 (uncoupling protein 1), WAT (white adipose tissues), FACS (fluorescence-activated cell sorting)Keywords
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Article info
Publication history
Published online: March 15, 2023
Accepted:
March 11,
2023
Received:
January 2,
2023
Identification
Copyright
© 2023 Elsevier Inc. All rights reserved.
