Resistin regulates the expression of plasminogen activator inhibitor-1 in 3T3-L1 adipocytes.

Abstract

Resistin and plasminogen activator inhibitor-1 (PAI-1) are adipokines, which are secreted from adipocytes. Increased plasma resistin and PAI-1 levels aggravate metabolic syndrome through exacerbation of insulin resistance and induction of chronic inflammation. However, the relationship between resistin and PAI-1 gene expression remains unclear. Previously, we found that resistin regulates lipid metabolism via carbohydrate responsive element-binding protein (ChREBP) during adipocyte maturation (Ikeda et al., 2013) [6]. In this study, to clarify the relationship between expression of resistin and PAI-1, PAI-1 expression in differentiated 3T3-L1 adipocytes was measured after transfection with anti-resistin siRNA. We found that PAI-1 gene expression and secreted PAI-1 protein were significantly decreased by resistin knockdown. Furthermore, phosphorylation of Akt, which can inhibit PAI-1 expression, was accelerated and the activity of protein phosphatase 2A (PP2A) was suppressed in resistin knockdown 3T3-L1 adipocytes. In addition, the expression of glucose transporter type 4, a ChREBP target gene, was reduced and was associated with inhibition of PP2A. The addition of culture medium collected from COS7 cells transfected with a resistin expression plasmid rescued the suppression of PAI-1 expression in resistin knockdown 3T3-L1 adipocytes. Our findings suggest that resistin regulates PAI-1 expression in 3T3-L1 adipocytes via Akt phosphorylation.

• Authors: Yoshito Ikeda, Hiroyuki Tsuchiya, Susumu Hama, Kazuaki Kajimoto, Kentaro Kogure
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 448 Issue 2 Pg. 129-33 (May 30 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24667608 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Culture Media, Conditioned
• Glucose Transporter Type 4
• Resistin
• Retn protein, mouse
• Serpin E2
• Serpine2 protein, mouse
• Slc2a4 protein, mouse
• Proto-Oncogene Proteins c-akt
• Protein Phosphatase 2

Topics

• 3T3-L1 Cells (drug effects)
• Adipocytes (physiology)
• Animals
• COS Cells
• Chlorocebus aethiops
• Culture Media, Conditioned (pharmacology)
• Gene Expression Regulation
• Gene Knockdown Techniques
• Glucose Transporter Type 4 (genetics, metabolism)
• Mice
• Phosphorylation
• Protein Phosphatase 2 (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Resistin (genetics, metabolism)
• Serpin E2 (genetics, metabolism)