Gene expression profile of adipocyte differentiation and its regulation by peroxisome proliferator-activated receptor-gamma agonists.
PPAR gamma is an adipocyte-specific nuclear hormone receptor. Agonists of PPAR gamma, such as thiazolidinediones (TZDs), promote adipocyte differentiation and have insulin-sensitizing effects in animals and diabetic patients. Affymetrix oligonucleotide arrays representing 6347 genes were employed to profile the gene expression responses of mature 3T3-L1 adipocytes and differentiating preadipocytes to a TZD PPAR gamma agonist in vitro. The expression of 579 genes was significantly up- or down-regulated by more than 1.5-fold during differentiation and/or by treatment with TZD, and these genes were organized into 32 clusters that demonstrated concerted changes in expression of genes controlling cell growth or lipid metabolism. Quantitative PCR was employed to further characterize gene expression and led to the identification of beta-catenin as a new PPAR gamma target gene. Both mRNA and protein levels for beta-catenin were down-regulated in 3T3-L1 adipocytes compared with fibroblasts and were further decreased by treatment of adipocytes with PPAR gamma agonists. Treatment of db/db mice with a PPAR gamma agonist also resulted in reduction of beta-catenin mRNA levels in adipose tissue. These results suggest that beta-catenin plays an important role in the regulation of adipogenesis. Thus, the transcriptional patterns revealed in this study further the understanding of adipogenesis process and the function of PPAR gamma activation.
Gerhold
David L
DL
Department of Pharmacology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Liu
Franklin
F
Jiang
Guoqiang
G
Li
Zhihua
Z
Xu
Jian
J
Lu
Meiqing
M
Sachs
Jeffrey R
JR
Bagchi
Ansuman
A
Fridman
Arthur
A
Holder
Daniel J
DJ
Doebber
Thomas W
TW
Berger
Joel
J
Elbrecht
Alex
A
Moller
David E
DE
Zhang
Bei B
BB
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D000465:Algorithms; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D017403:In Situ Hybridization; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D015345:Oligonucleotide Probes; D010641:Phenotype; D012313:RNA; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D015534:Trans-Activators; D014157:Transcription Factors / Q000819:agonists* / Q000502:physiology*; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D007004:Hypoglycemic Agents; D015345:Oligonucleotide Probes; C034477:RNA primers; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D000077154:Rosiglitazone; D012313:RNA