Rapamycin inhibits clonal expansion and adipogenic differentiation of 3T3-L1 cells

Wen Chen Yeh, Barbara E. Bierer, Steven L. McKnight

Research output: Contribution to journalArticle

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Abstract

Differentiating 3T3-L1 cells express an immunophilin early during the adipocyte conversion program as described in this issue [Yeh, W.-C., Li, T.-K., Bierer, B. E. & McKnight, S. L. (1995) Proc. Natl. Acad. Sci. USA 92, 11081-11085]. The temporal expression profile of this protein, designated FK506-binding protein (FKBP) 51, is concordant with the clonal-expansion period undertaken by 3T3-L1 cells after exposure to adipogenic hormones. Having observed FKBP51 synthesis early during adipogenesis, we tested the effects of three immunosuppressive drugs - cyclosporin A, FK506, and rapamycin - on the terminal-differentiation process. Adipocyte conversion was not affected by either cyclosporin A or FK506 and yet was significantly reduced by rapamycin at drug concentrations as low as 10 nM. Clonal expansion was impeded in drug-treated cultures, as was the accumulation of cytoplasmic lipid droplets normally seen late during differentiation. Rapamycin treatment likewise inhibited the expression of CCAAT/enhancer binding protein α, a transcription factor required for 3T3-L1 cell differentiation. All three of these effects were reversed by high FK506 concentrations, indicating that the operative inhibitory event was mediated by an immunophilin-rapamycin complex.

Original languageEnglish (US)
Pages (from-to)11086-11090
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number24
StatePublished - Nov 21 1995

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3T3-L1 Cells
Sirolimus
Tacrolimus
Immunophilins
Adipocytes
Cyclosporine
Pharmaceutical Preparations
Tacrolimus Binding Proteins
CCAAT-Enhancer-Binding Proteins
Adipogenesis
Immunosuppressive Agents
Cell Differentiation
Transcription Factors
Hormones
Proteins

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Rapamycin inhibits clonal expansion and adipogenic differentiation of 3T3-L1 cells. / Yeh, Wen Chen; Bierer, Barbara E.; McKnight, Steven L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 24, 21.11.1995, p. 11086-11090.

Research output: Contribution to journalArticle

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