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Updated: Jul 15, 2026
Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
Fat-specific FUS-DDIT3-transgenic mice establish PPARgamma inactivation is required to liposarcoma development
Pedro Antonio Pérez-Mancera1, Carolina Vicente-Dueñas, Inés González-Herrero
1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas/Universidad de Salamanca, Campus Unamuno, 37007 Salamanca, Spain.
Abstract:
FUS-DDIT3 is a chimeric oncogene generated by the most common chromosomal translocation t(12;16)(q13;p11) associated to liposarcomas. The application of transgenic methods and the use of primary mesenchymal progenitor cells to the study of this sarcoma-associated FUS-DDIT3 gene fusion have provided insights into their in vivo functions and suggested mechanisms by which lineage selection may be achieved. These studies indicate that FUS-DDIT3 contributes to differentiation arrest acting at a point in the adipocyte differentiation process after induction of peroxisome proliferator-activated receptor gamma (PPARgamma) expression. To test this idea within a living mouse, we generated mice expressing FUS-DDIT3 within aP2-positive cells, because aP2 is a downstream target of PPARgamma expressed at the immature adipocyte stage. Here, we report that FUS-DDIT3 expression was successfully induced at the aP2 stage of differentiation both in vivo and in vitro. aP2-FUS-DDIT3 mice do not develop liposarcomas and exhibit an increase in white adipose tissue size. Consistent with in vivo data, mouse embryonic fibroblasts (MEFs) obtained from aP2-FUS-DDIT3 mice not only were capable of terminal differentiation but also showed an increased capacity for adipogenesis in vitro compared with wild-type MEFs. Taken together, this study provides genetic evidence that the presence of FUS-DDIT3 in an aP2-positive cell is not enough to cause liposarcoma development and establishes that PPARgamma inactivation is required for liposarcoma development.
Insights
The FUS-DDIT3 gene fusion, linked to liposarcoma, does not cause cancer in mice when expressed in adipocyte precursor cells. PPARgamma inactivation is necessary for liposarcoma development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- FUS-DDIT3 is a chimeric oncogene resulting from the t(12;16)(q13;p11) translocation, commonly found in liposarcomas.
- Previous studies suggest FUS-DDIT3 induces differentiation arrest in adipocyte development after PPARgamma expression.
Purpose of the Study:
- To investigate the in vivo role of FUS-DDIT3 in adipocyte differentiation and liposarcoma development.
- To determine if FUS-DDIT3 expression in aP2-positive cells is sufficient to cause liposarcoma.
Main Methods:
- Generation of transgenic mice (aP2-FUS-DDIT3) expressing FUS-DDIT3 in aP2-positive cells.
- In vivo and in vitro studies using these mice and their derived embryonic fibroblasts (MEFs).
Main Results:
- FUS-DDIT3 expression was successfully induced at the immature adipocyte (aP2) stage.
- aP2-FUS-DDIT3 mice did not develop liposarcomas but showed increased white adipose tissue.
- MEFs from these mice exhibited normal terminal differentiation and enhanced adipogenesis.
Conclusions:
- FUS-DDIT3 expression alone in aP2-positive cells is insufficient for liposarcoma formation.
- PPARgamma inactivation is a critical requirement for the development of liposarcoma in the context of FUS-DDIT3 expression.
