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PMID:12055200

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Citation

Bennett, CN, Ross, SE, Longo, KA, Bajnok, L, Hemati, N, Johnson, KW, Harrison, SD and MacDougald, OA (2002) Regulation of Wnt signaling during adipogenesis. J. Biol. Chem. 277:30998-1004

Abstract

We have identified Wnt10b as a potent inhibitor of adipogenesis that must be suppressed for preadipocytes to differentiate in vitro. Here, we demonstrate that a specific inhibitor of glycogen synthase kinase 3, CHIR 99021, mimics Wnt signaling in preadipocytes. CHIR 99021 stabilizes free cytosolic beta-catenin and inhibits adipogenesis by blocking induction of CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma. Preadipocyte differentiation is inhibited when 3T3-L1 cells are exposed to CHIR 99021 for any 24 h period during the first 3 days of adipogenesis. Consistent with this time frame of inhibition, expression of Wnt10b mRNA is suppressed upon induction of differentiation, with a 50% decline by 6 h and complete inhibition by 36 h. Of the agents used to induce differentiation, exposure of 3T3-L1 cells to methyl-isobutylxanthine or cAMP is sufficient to suppress expression of Wnt10b mRNA. Inhibition of adipogenesis by Wnt10b is likely mediated by Wnt receptors, Frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 6. These receptors, like Wnt10b, are highly expressed in preadipocytes and stromal vascular cells. Finally, we demonstrate that disruption of extracellular Wnt signaling by expression of secreted Frizzled related proteins causes spontaneous adipocyte conversion.

Links

PubMed Online version:10.1074/jbc.M204527200

Keywords

3T3 Cells; Adipocytes/physiology; Animals; CCAAT-Enhancer-Binding Protein-alpha/antagonists & inhibitors; Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors; Cell Differentiation; Cyclic AMP/physiology; Enzyme Inhibitors/pharmacology; Glycogen Synthase Kinase 3; Glycogen Synthase Kinases; Mice; Proto-Oncogene Proteins/physiology; Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors; Stem Cells/physiology; Transcription Factors/antagonists & inhibitors; Wnt Proteins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:WN10B

acts_upstream_of_or_within

GO:0045599: negative regulation of fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

  • regulates_o_results_in_acquisition_of_features_of:(CL:0000136)

Seeded From UniProt

complete

MOUSE:WN10B

acts_upstream_of_or_within

GO:0071320: cellular response to cAMP

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000136)

Seeded From UniProt

complete

MOUSE:WN10B

acts_upstream_of_or_within

GO:0071310: cellular response to organic substance

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000136)

Seeded From UniProt

complete

MOUSE:SFRP3

acts_upstream_of_or_within

GO:0045600: positive regulation of fat cell differentiation

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:Q92765

P

Seeded From UniProt

complete

MOUSE:CTNB1

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CTNB1

located_in

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SFRP1

acts_upstream_of_or_within

GO:0045600: positive regulation of fat cell differentiation

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:Q8N474

P

Seeded From UniProt

complete

MOUSE:DKKL1

acts_upstream_of_or_within

GO:0045600: positive regulation of fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WIF1

acts_upstream_of_or_within

GO:0045600: positive regulation of fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SFRP2

involved_in

GO:0045600: positive regulation of fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SFRP2

acts_upstream_of_or_within

GO:0045600: positive regulation of fat cell differentiation

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:Q96HF1

P

Seeded From UniProt

complete

MOUSE:GSK3A

acts_upstream_of_or_within

GO:0071407: cellular response to organic cyclic compound

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PPARG

acts_upstream_of_or_within

GO:0071407: cellular response to organic cyclic compound

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CTNB1

part_of

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CTNB1

part_of

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SFRP3

involved_in

GO:0045600: positive regulation of fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CEBPA

acts_upstream_of_or_within

GO:0071407: cellular response to organic cyclic compound

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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