Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte phenotype and survival.
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.
Chawla
A
A
Department of Medicine and Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104.
Lazar
M A
MA
D016475:3T3 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002994:Clofibrate / Q000494:pharmacology; D003470:Culture Media; D051379:Mice; D008830:Microbodies / Q000187:drug effects; D010641:Phenotype; D011743:Pyrimidines / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
D003470:Culture Media; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D015117:5,8,11,14-Eicosatetraynoic Acid; D014212:Tretinoin; C006253:pirinixic acid; D002994:Clofibrate