Biochemical correlates of thiazolidinedione-induced adipocyte differentiation by high-resolution magic angle spinning NMR spectroscopy Journal Article


Authors: Chen, J. H.; Enloe, B. M.; Weybright, P.; Campbell, N.; Dorfman, D.; Fletcher, C. D.; Cory, D. G.; Singer, S.
Article Title: Biochemical correlates of thiazolidinedione-induced adipocyte differentiation by high-resolution magic angle spinning NMR spectroscopy
Abstract: Thiazolidinediones, a class of synthetic ligands to the peroxisome proliferator-activated receptor-γ, induce terminal adipocyte differentiation of 3T3 F442A cells, and have already been used as alternative therapeutic agents for the treatment of liposarcoma in clinical trials. The biochemical changes occurring in the 3T3 F442A cell line and well-differentiated liposarcoma following induction of adipocyte differentiation with the thiazolidinedione troglitazone were measured using high-resolution magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy. 3T3 F442A cell differentiation was characterized by a large accumulation of intracellular triglyceride and withdrawal from the cell cycle. Phosphatidylcholine (PTC), phosphocholine (PC), myo-inositol, and glycerol were found to be possible biochemical markers for adipocyte differentiation induced by thiazolidenediones. The molar ratio of PTC to PC increased fourfold in differentiated 3T3 F442A cells compared to undifferentiated cells, suggesting a substantial increase in CTP:phosphocholine cytidylyltransferase activity with differentiation. A 2.8-fold increase in the PTC:PC ratio was observed in the lipoma-like well-differentiated liposarcoma of three patients who were treated with troglitazone when compared to liposarcoma from patients not treated with this drug. Thus, this ratio may be an NMR-detectable marker of troglitazone efficacy and response to differentiation therapy for liposarcoma. © 2002 Wiley-Liss, Inc.
Keywords: controlled study; human tissue; human cell; nonhuman; antineoplastic agents; flow cytometry; animal cell; animals; mice; cells, cultured; cell cycle; cell differentiation; drug effect; transcription factors; correlation analysis; image quality; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; ligands; triacylglycerol; thiazoles; peroxisome proliferator activated receptor gamma; inositol; cell strain 3t3; phosphatidylcholine; liposarcoma; 3t3 cells; receptors, cytoplasmic and nuclear; phosphorylcholine; adipocyte; glycerol; adipocytes; thiazolidinediones; 2,4 thiazolidinedione derivative; phosphatidylcholines; biochemical marker; troglitazone; chromans; nmr spectroscopy; humans; human; article; 3t3 f442a; ctp:phosphocholine cytidylyltransferase
Journal Title: Magnetic Resonance in Medicine
Volume: 48
Issue: 4
ISSN: 0740-3194
Publisher: John Wiley & Sons  
Date Published: 2002-10-01
Start Page: 602
End Page: 610
Language: English
DOI: 10.1002/mrm.10256
PUBMED: 12353276
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus
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  1. Jinhong Chen
    17 Chen
  2. Samuel Singer
    338 Singer