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

Publication ,  Journal Article
Ye, R; Wang, QA; Tao, C; Vishvanath, L; Shao, M; McDonald, JG; Gupta, RK; Scherer, PE
Published in: Mol Metab
November 2015

BACKGROUND: The selective estrogen receptor modulator tamoxifen, in combination with the Cre-ER(T2) 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-ER(T2) 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.

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Published In

Mol Metab

DOI

ISSN

2212-8778

Publication Date

November 2015

Volume

4

Issue

11

Start / End Page

771 / 778

Location

Germany

Related Subject Headings

  • 3101 Biochemistry and cell biology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology
 

Citation

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Ye, R., Wang, Q. A., Tao, C., Vishvanath, L., Shao, M., McDonald, J. G., … Scherer, P. E. (2015). Impact of tamoxifen on adipocyte lineage tracing: Inducer of adipogenesis and prolonged nuclear translocation of Cre recombinase. Mol Metab, 4(11), 771–778. https://doi.org/10.1016/j.molmet.2015.08.004
Ye, Risheng, Qiong A. Wang, Caroline Tao, Lavanya Vishvanath, Mengle Shao, Jeffery G. McDonald, Rana K. Gupta, and Philipp E. Scherer. “Impact of tamoxifen on adipocyte lineage tracing: Inducer of adipogenesis and prolonged nuclear translocation of Cre recombinase.Mol Metab 4, no. 11 (November 2015): 771–78. https://doi.org/10.1016/j.molmet.2015.08.004.
Ye R, Wang QA, Tao C, Vishvanath L, Shao M, McDonald JG, et al. Impact of tamoxifen on adipocyte lineage tracing: Inducer of adipogenesis and prolonged nuclear translocation of Cre recombinase. Mol Metab. 2015 Nov;4(11):771–8.
Ye, Risheng, et al. “Impact of tamoxifen on adipocyte lineage tracing: Inducer of adipogenesis and prolonged nuclear translocation of Cre recombinase.Mol Metab, vol. 4, no. 11, Nov. 2015, pp. 771–78. Pubmed, doi:10.1016/j.molmet.2015.08.004.
Ye R, Wang QA, Tao C, Vishvanath L, Shao M, McDonald JG, Gupta RK, Scherer PE. Impact of tamoxifen on adipocyte lineage tracing: Inducer of adipogenesis and prolonged nuclear translocation of Cre recombinase. Mol Metab. 2015 Nov;4(11):771–778.
Journal cover image

Published In

Mol Metab

DOI

ISSN

2212-8778

Publication Date

November 2015

Volume

4

Issue

11

Start / End Page

771 / 778

Location

Germany

Related Subject Headings

  • 3101 Biochemistry and cell biology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology