Inhibition of adipogenesis by RGD-dependent disintegrin
Journal
Biochemical Pharmacology
Journal Volume
70
Journal Issue
10
Pages
1469-1478
Date Issued
2005
Author(s)
Abstract
Adipogenesis plays a central role in obesity development. The processes of adipogenesis include migration, adhesion, proliferation and survival of preadipocytes and differentiation to mature adipocytes. Many of these biological functions are related to integrins. Here, we found that snake venom-derived arginine-glycine-aspartic acid (RGD)-containing disintegrin inhibited adipogenesis. Rhodostomin but not rhodostomin RGD mutants (RGE-Rn and AKGDWN-Rn) caused the detachment of primary cultured preadipocyte. Furthermore, rhodostomin also inhibited focal adhesion of preadipocyte, including the inhibition of the expression of focal adhesion kinase (FAK) and FAK phosphorylation, assembly of vinculin and reorganization of actin cytoskeleton. Cell viability of preadipocytes was decreased after rhodostomin treatment in a concentration-dependent manner. The results of flow cytometric analysis showed that rhodostomin induced cell apoptosis. In addition, chromatin condensation was observed in DAPI staining. The increase of Bax expression and activation of capsase-3 was detected following rhodostomin treatment. Addition of dexamethasone, IBMX and insulin induced differentiation of preadipocytes into mature adipocytes and treatment of cells with rhodostomin during the initial 3 days showed less mature adipocytes following 9-10 days of differentiating period. The triglyceride content and gene expression of peroxisome proliferators-activated receptor gamma (PPARγ) and leptin also decreased in response to the treatment of rhodostomin. These results suggest that disintegrin inhibits processes of adipogenesis and may be developed to treat obesity. ? 2005 Elsevier Inc. All rights reserved.
SDGs
Other Subjects
actin; alanyllysylglycylaspartyltryptophylasparagine; arginylglycylaspartic acid; caspase 3; dexamethasone; disintegrin; focal adhesion kinase; hexapeptide; insulin; isobutylmethylxanthine; leptin; peroxisome proliferator activated receptor gamma; protein Bax; rhodostomin; snake venom; triacylglycerol; unclassified drug; vinculin; animal cell; apoptosis; article; cell culture; cell differentiation; cell viability; chromatin condensation; concentration response; controlled study; cytoskeleton; drug effect; enzyme activation; enzyme inhibition; enzyme phosphorylation; flow cytometry; focal adhesion; gene expression; nonhuman; obesity; priority journal; proadipocyte; protein expression; rat; staining; Actins; Adipocytes; Adipogenesis; Animals; Apoptosis; Cell Culture Techniques; Cell Differentiation; Cells, Cultured; Crotalid Venoms; Cytoskeleton; Disintegrins; Dose-Response Relationship, Drug; Focal Adhesion Protein-Tyrosine Kinases; Integrin alphaVbeta3; Leptin; Oligopeptides; Peptides; PPAR gamma; Rats; RNA, Messenger; Vinculin
Type
journal article