Research Article| Volume 143, 155536, June 2023

Involvement of a novel cAMP signaling mediator for beige adipogenesis


      • 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.



      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.


      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.


      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.


      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

      Unlabelled Image
      Graphical AbstractPROM1-ERM axis in adipogenic progenitor cells is critical in ensuing beige adipogenesis in response to cold stimulus during adaptive thermogenesis.


      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)


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