Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte phenotype and survival

Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1786-90. doi: 10.1073/pnas.91.5.1786.

Abstract

Culture of mouse 3T3-L1 preadipocytes in medium containing delipidated bovine calf serum caused the cells to elongate and divide after reaching confluency. The continued proliferation correlated with sustained expression of the c-myc gene, which was repressed in control cells. Exposure of the cells to activators of peroxisome proliferator-activated receptor (PPAR), including clofibrate, WY-14,643, and 5,8,11,14-eicosatetraynoic acid, reversed and prevented the effects of culturing preadipocytes in delipidated serum. Continued exposure to PPAR activators led to adipose conversion, during which PPAR and its heterodimerization partner (retinoid X receptor) were induced. Retinoic acid (RA) had no effect on the growth or survival of preadipocytes grown in the presence of normal bovine serum. However, treatment of cells cultured in delipidated serum with RA caused death of the cells by apoptosis. Thus, preadipocyte phenotype and survival are regulated by activators of nuclear hormone receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells / cytology
  • 3T3 Cells / drug effects
  • 3T3 Cells / metabolism
  • 5,8,11,14-Eicosatetraynoic Acid / pharmacology
  • Adipose Tissue / cytology
  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Animals
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Clofibrate / pharmacology
  • Culture Media
  • Mice
  • Microbodies / drug effects
  • Phenotype
  • Pyrimidines / pharmacology
  • Receptors, Cytoplasmic and Nuclear / drug effects
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Retinoic Acid*
  • Retinoid X Receptors
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Transcription Factors / drug effects
  • Transcription Factors / metabolism*
  • Tretinoin / pharmacology*

Substances

  • Culture Media
  • Pyrimidines
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Transcription Factors
  • 5,8,11,14-Eicosatetraynoic Acid
  • Tretinoin
  • pirinixic acid
  • Clofibrate