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PMID:19837878

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Citation

Suzuki, M, Setsuie, R and Wada, K (2009) Ubiquitin carboxyl-terminal hydrolase l3 promotes insulin signaling and adipogenesis. Endocrinology 150:5230-9

Abstract

Insulin is a potent adipogenic hormone that triggers the induction of a series of transcription factors and specific proteins governing the differentiation of preadipocytes into mature adipocytes. Here we report that ubiquitin carboxyl-terminal hydrolase (UCH)-L3, a deubiquitinating enzyme, promotes insulin signaling and adipogenesis. Uchl3(-/-) mice had less visceral white adipose tissue compared with wild-type mice. In vitro adipogenesis experiments revealed that mouse embryonic fibroblasts (MEFs) and preadipocytes from Uchl3(-/-) mice had impaired ability to differentiate into mature adipocytes than those from wild-type mice. This difference was diminished by removing insulin from the medium. RT-PCR analysis showed that insulin-regulated expression of srebp1c, fas, glut4, and adiponectin is impaired in Uchl3(-/-) cells. The phosphorylation of insulin/IGF-I receptor, Akt, glycogen synthase kinase-3beta, and FoxO1 was decreased in Uchl3(-/-) MEFs treated with insulin. Moreover, ectopic expression of wild-type UCH-L3 restored the phosphorylation of insulin/IGF-I receptor and adipocyte differentiation in Uchl3(-/-) MEFs. In contrast, hydrolase activity-deficient UCH-L3 did not enhance insulin signaling and the expression of glut4, fabp4, and adiponectin, resulting in impaired formation of large lipid droplets. These results suggest that UCH-L3 promotes adipogenesis by enhancing insulin signaling in a hydrolase activity-dependent manner.

Links

PubMed Online version:10.1210/en.2009-0332

Keywords

Adipocytes/cytology; Adipocytes/metabolism; Adipogenesis/genetics; Adipogenesis/physiology; Adiponectin/genetics; Adipose Tissue, White/metabolism; Animals; Antigens, CD95/genetics; Cell Differentiation/genetics; Cell Differentiation/physiology; Cells, Cultured; Embryo, Mammalian/cytology; Fibroblasts/cytology; Fibroblasts/metabolism; Gene Expression; Glucose Transporter Type 4/genetics; Immunoblotting; Male; Mice; Mice, Knockout; Phosphorylation; Proto-Oncogene Proteins c-akt/metabolism; Receptor, IGF Type 1/metabolism; Receptor, Insulin/genetics; Receptor, Insulin/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Sterol Regulatory Element Binding Protein 1/genetics; Ubiquitin Thiolesterase/genetics; Ubiquitin Thiolesterase/metabolism

Significance

Annotations

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

MOUSE:UCHL3

involved_in

GO:0032869: cellular response to insulin stimulus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:UCHL3

involved_in

GO:0045600: positive regulation of fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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