Journal
MOLECULAR METABOLISM
Volume 4, Issue 11, Pages 771-778Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molmet.2015.08.004
Keywords
Tamoxifen; Cre recombinase; Adipose tissue; Lineage tracing
Categories
Funding
- NHLBI NIH HHS [P01 HL020948] Funding Source: Medline
- NIDDK NIH HHS [R01 DK099110, R01 DK104789, R03 DK099428, P01 DK088761, R01 DK055758] Funding Source: Medline
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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 PPAR gamma 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. (C) 2015 The Authors. Published by Elsevier GmbH.
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