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PMID: 8127882 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Chawla A, Lazar MA

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.

MeSH Terms
3T3 Cells/cytology,drug effects,metabolism 5,8,11,14-Eicosatetraynoic Acid/pharmacology Adipose Tissue/cytology,drug effects,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,metabolism Receptors, Retinoic Acid Retinoid X Receptors Signal Transduction Stem Cells/cytology,drug effects,metabolism Transcription Factors/drug effects,metabolism Tretinoin/pharmacology
Chemicals
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
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Chawla A
Department of Medicine and Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104.
Lazar M A
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36 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1994-03-01
Pages
1786-90
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC43248
Subset
IM
Grants
NIDDK NIH HHS · DK45586 · United States
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