| Pigment epithelium-derived factor (PEDF) is one of the most abundant proteins secreted by human adipocytes and induces insulin resistance and inflammatory signaling in muscle and fat cells. | |
| | |
MedLine Citation:
|
PMID: 20938440 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
Objective:Pigment epithelium-derived factor (PEDF) is a multifunctional protein with neurotrophic and anti-angiogenic properties. More recently it became evident that PEDF is upregulated in patients with type 2 diabetes and also contributes to insulin resistance in mice. During characterization of the secretome of in vitro differentiated human adipocytes by two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization-MS, we found that PEDF is one of the most abundant proteins released by adipocytes. The aim of this study was to investigate the regulation and autocrine function of PEDF in human adipocytes and to determine its paracrine effects on human skeletal muscle cells (hSkMC) and human smooth muscle cells (hSMC).Methods and results:Human primary adipocytes secrete 130 ng ml(-1) PEDF over 24 h from 1 million cells, which is extremely high as compared with adiponectin, interleukin-6 (IL-6) or IL-8. This release of PEDF is significantly higher than from other primary cells, such as adipose-tissue located macrophages (50-times), hSkMC and hSMC (5-times). PEDF protein expression significantly increases during adipogenesis, which is paralleled by increased PEDF secretion. Furthermore, tumor necrosis factor-α and hypoxia significantly downregulate PEDF protein levels. PEDF secretion was significantly reduced by troglitazone and hypoxia and significantly increased by insulin. Treatment of adipocytes and hSkMC with PEDF induced insulin resistance in adipocytes, skeletal and smooth muscle cells at the level of insulin-stimulated Akt phosphorylation, which was dose dependent and more prominent in adipocytes. Furthermore, inflammatory nuclear factor-κB (NF-κB) signaling was induced by PEDF. In hSMC, PEDF induced proliferation (1.7-fold) and acutely activated proliferative and inflammatory signaling pathways (NF-κB, p38 mitogen-activated protein kinase and mammalian target of rapamycin).Conclusion:PEDF is one of the most abundant adipokines and its secretion is inversely regulated by insulin and hypoxia. PEDF induces insulin resistance in adipocytes and hSkMC and leads to inflammatory signaling in hSMC. Because of these diverse actions, PEDF is a key adipokine, which could have an important role in diabetes and obesity-related disorders. |
| | |
Authors:
|
S Famulla; D Lamers; S Hartwig; W Passlack; A Horrighs; A Cramer; S Lehr; H Sell; J Eckel |
Publication Detail:
|
Type: Journal Article Date: 2010-10-12 |
Journal Detail:
|
Title: International journal of obesity (2005) Volume: 35 ISSN: 1476-5497 ISO Abbreviation: Int J Obes (Lond) Publication Date: 2011 Jun |
Date Detail:
|
Created Date: 2011-06-14 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101256108 Medline TA: Int J Obes (Lond) Country: England |
Other Details:
|
Languages: eng Pagination: 762-72 Citation Subset: IM |
Affiliation:
|
Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metaboli...
Next Document: Pancreatic acinar cell-specific overexpression of group 1B phospholipase A2 exacerbates diet-induced...