P53 is required for brown adipogenic differentiation and has a protective role against diet-induced obesity

A. Molchadsky, O. Ezra, P. G. Amendola, D. Krantz, I. Kogan-Sakin, Y. Buganim, N. Rivlin, N. Goldfinger, V. Folgiero, R. Falcioni, R. Sarig, V. Rotter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Proper regulation of white and brown adipogenic differentiation is important for maintaining an organism's metabolic profile in a homeostatic state. The recent observations showing that the p53 tumor suppressor plays a role in metabolism raise the question of whether it is involved in the regulation of white and brown adipocyte differentiation. By using several in vitro models, representing various stages of white adipocyte differentiation, we found that p53 exerts a suppressive effect on white adipocyte differentiation in both mouse and human cells. Moreover, our in vivo analysis indicated that p53 is implicated in protection against diet-induced obesity. In striking contrast, our data shows that p53 exerts a positive regulatory effect on brown adipocyte differentiation. Abrogation of p53 function in skeletal muscle committed cells reduced their capacity to differentiate into brown adipocytes and histological analysis of brown adipose tissue revealed an impaired morphology in both embryonic and adult p53-null mice. Thus, depending on the specific adipogenic differentiation program, p53 may exert a positive or a negative effect. This cell type dependent regulation reflects an additional modality of p53 in maintaining a homeostatic state, not only in the cell, but also in the organism at large.

Original languageAmerican English
Pages (from-to)774-783
Number of pages10
JournalCell Death and Differentiation
Volume20
Issue number5
DOIs
StatePublished - May 2013
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements. This research was supported by a Center of Excellence grant from Flight Attendant Medical Research Institute (FAMRI), Yad Abraham Center for Cancer Diagnosis and Therapy and by EC FP7-INFLACARE number-223151. VR is the incumbent of the Norman and Helen Asher Professorial Chair Cancer Research at the Weizmann institute. ED is the incumbent of the Henry J Leir Professorial Chair. We are grateful to Dr. Ori Brenner for pathological analysis and to Dr. Inbal Biton and Dr. Michael Tzoory for technical assistance.

Keywords

  • development
  • obesity
  • p53
  • white and brown adipogenesis

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