Impact of tamoxifen on adipocyte lineage tracing: Inducer of adipogenesis and prolonged nuclear translocation of Cre recombinase

Risheng Ye, Qiong A. Wang, Caroline Tao, Lavanya Vishvanath, Mengle Shao, Jeffrey G McDonald, Rana K Gupta, Philipp E Scherer

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Background: The selective estrogen receptor modulator tamoxifen, in combination with the Cre-ERT2 fusion protein, has been one of the mainstream methods to induce genetic recombination and has found widespread application in lineage tracing studies. Methods & results: Here, we report that tamoxifen exposure at widely used concentrations remains detectable by mass-spectrometric analysis in adipose tissue after a washout period of 10 days. Surprisingly, its ability to maintain nuclear translocation of the Cre-ERT2 protein is preserved beyond 2 months of washout. Tamoxifen treatment acutely leads to transient lipoatrophy, followed by de novo adipogenesis that reconstitutes the original fat mass. In addition, we find a "synthetically lethal" phenotype for adipocytes when tamoxifen treatment is combined with adipocyte-specific loss-of-function mutants, such as an adipocyte-specific PPARγ knockout. This is observed to a lesser extent when alternative inducible approaches are employed. Conclusions: These findings highlight the potential for tamoxifen-induced adipogenesis, and the associated drawbacks of the use of tamoxifen in lineage tracing studies, explaining the discrepancy in lineage tracing results from different systems with temporal control of gene targeting.

Original languageEnglish (US)
Pages (from-to)771-778
Number of pages8
JournalMolecular Metabolism
Volume4
Issue number11
DOIs
StatePublished - Nov 2015

Keywords

  • Adipose tissue
  • Cre recombinase
  • Lineage tracing
  • Tamoxifen

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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